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1. Diversity of Methicillin-Resistant Staphylococcus aureus Strains Isolated from Residents of 26 Nursing Homes in Orange County, California

Author

Hudson, Lyndsey O, Reynolds, Courtney, Spratt, Brian G, Enright, Mark C, Quan, Victor, Kim, Diane, Hannah, Paul, Mikhail, Lydia, Alexander, Richard, Moore, Douglas F, Godoy, Daniel, Bishop, Cynthia J, and Huang, Susan S

Subjects
Clinical Research, Emerging Infectious Diseases, Infectious Diseases, Antimicrobial Resistance, Aging, Aetiology, 2.2 Factors relating to the physical environment, Aged, Aged, 80 and over, California, Female, Genetic Variation, Genotype, Hospitals, Humans, Male, Methicillin-Resistant Staphylococcus aureus, Middle Aged, Molecular Epidemiology, Molecular Typing, Nasal Cavity, Nursing Homes, Prevalence, Prospective Studies, Staphylococcal Infections, Staphylococcal Protein A, meticillin, adolescent, adult, aged, article, bacterial gene, bacterial strain, bacterium carrier, bacterium identification, bacterium isolate, bacterium isolation, child, controlled study, female, frequency analysis, gene sequence, genetic heterogeneity, genetic variability, hospital admission, hospital patient, human, male, methicillin resistant Staphylococcus aureus, microbial diversity, nonhuman, nose smear, nursing home, nursing home patient, population research, prevalence, priority journal, prospective study, spa gene, strain difference, United States, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Microbiology
Abstract

Nursing homes represent a unique and important methicillin-resistant Staphylococcus aureus (MRSA) reservoir. Not only are strains imported from hospitals and the community, strains can be transported back into these settings from nursing homes. Since MRSA bacteria are prevalent in nursing homes and yet relatively poorly studied in this setting, a multicenter, regional assessment of the frequency and diversity of MRSA in the nursing home reservoir was carried out and compared to that of the MRSA from hospitals in the same region. The prospective study collected MRSA from nasal swabbing of residents of 26 nursing homes in Orange County, California, and characterized each isolate by spa typing. A total of 837 MRSA isolates were collected from the nursing homes. Estimates of admission prevalence and point prevalence of MRSA were 16% and 26%, respectively. The spa type genetic diversity was heterogeneous between nursing homes and significantly higher overall (77%) than the diversity in Orange County hospitals (72%). MRSA burden in nursing homes appears largely due to importation from hospitals. As seen in Orange County hospitals, USA300 (sequence type 8 [ST8]/t008), USA100 (ST5/t002), and a USA100 variant (ST5/t242) were the dominant MRSA clones in Orange County nursing homes, representing 83% of all isolates, although the USA100 variant was predominant in nursing homes, whereas USA300 was predominant in hospitals. Control strategies tailored to the complex problem of MRSA transmission and infection in nursing homes are needed in order to minimize the impact of this unique reservoir on the overall regional MRSA burden.

Published
2013

2. Predictors of Hospitals with Endemic Community-Associated Methicillin-Resistant Staphylococcus aureus

Author

Murphy, Courtney R, Hudson, Lyndsey O, Spratt, Brian G, Elkins, Kristen, Terpstra, Leah, Gombosev, Adrijana, Nguyen, Christopher, Hannah, Paul, Alexander, Richard, Enright, Mark C, and Huang, Susan S

Subjects
Emerging Infectious Diseases, Vaccine Related, Prevention, Clinical Research, Infectious Diseases, Antimicrobial Resistance, Biodefense, 2.2 Factors relating to the physical environment, Aetiology, Adolescent, Adult, Aged, Aged, 80 and over, California, Carrier State, Community-Acquired Infections, Comorbidity, Female, Hospital Bed Capacity, Hospitals, Humans, Male, Medicaid, Methicillin-Resistant Staphylococcus aureus, Middle Aged, Prevalence, Prospective Studies, Staphylococcal Infections, United States, Young Adult, adult, aged, article, bacterium isolate, cohort analysis, community associated methicillin resistant Staphylococcus aureus infection, comorbidity, endemic disease, female, gender, hospital, hospital infection, hospital patient, human, major clinical study, male, methicillin resistant Staphylococcus aureus infection, molecular typing, multilocus sequence typing, prediction, prospective study, Medical and Health Sciences, Epidemiology
Abstract

ObjectiveWe sought to identify hospital characteristics associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage among inpatients.Design Prospective cohort study.Setting Orange County, California.Participants Thirty hospitals in a single county.Methods We collected clinical MRSA isolates from inpatients in 30 of 31 hospitals in Orange County, California, from October 2008 through April 2010. We characterized isolates by spa typing to identify CA-MRSA strains. Using California's mandatory hospitalization data set, we identified hospital-level predictors of CA-MRSA isolation.Results CA-MRSA strains represented 1,033 (46%) of 2,246 of MRSA isolates. By hospital, the median percentage of CA-MRSA isolates was 46% (range, 14%-81%). In multivariate models, CA-MRSA isolation was associated with smaller hospitals (odds ratio [OR], 0.97, or 3% decreased odds of CA-MRSA isolation per 1,000 annual admissions; P < .001, hospitals with more Medicaid-insured patients (OR, 1.2; P = .002), and hospitals with more patients with low comorbidity scores (OR, 1.3; P < .001). Results were similar when restricted to isolates from patients with hospital-onset infection.Conclusions Among 30 hospitals, CA-MRSA comprised nearly half of MRSA isolates. There was substantial variability in CA-MRSA penetration across hospitals, with more CA-MRSA in smaller hospitals with healthier but socially disadvantaged patient populations. Additional research is needed to determine whether infection control strategies can be successful in targeting CA-MRSA influx.

Published
2013

3. Diversity of Methicillin-Resistant Staphylococcus aureus (MRSA) Strains Isolated from Inpatients of 30 Hospitals in Orange County, California

Author

Hudson, Lyndsey O, Murphy, Courtney R, Spratt, Brian G, Enright, Mark C, Elkins, Kristen, Nguyen, Christopher, Terpstra, Leah, Gombosev, Adrijana, Kim, Diane, Hannah, Paul, Mikhail, Lydia, Alexander, Richard, Moore, Douglas F, Huang, Susan S, and de Lencastre, Herminia

Subjects
Panton-Valentine Leukocidin, Field Gel-Electrophoresis, Care-Associated Infection, Soft-Tissue Infections, Health-Care, United-States, Nosocomial Transmission, Molecular Epidemiology, Emergency-Department, Typing Methods
Published
2013

4. Predicting high prevalence of community methicillin-resistant Staphylococcus aureus strains in nursing homes.

Author

Murphy, Courtney R, Hudson, Lyndsey O, Spratt, Brian G, Quan, Victor, Kim, Diane, Peterson, Ellena, Tan, Grace, Evans, Kaye, Meyers, Hildy, Cheung, Michele, Lee, Bruce Y, Mukamel, Dana B, Enright, Mark C, Whealon, Matthew, and Huang, Susan S

Subjects
Nose, Humans, Staphylococcal Infections, Community-Acquired Infections, Prevalence, Multivariate Analysis, Odds Ratio, Carrier State, Age Factors, Aged, Middle Aged, Hispanic Americans, Nursing Homes, California, Female, Male, Methicillin-Resistant Staphylococcus aureus, staphylococcus protein A, adolescent, adult, article, bacterium identification, child, community associated methicillin resistant Staphylococcus aureus, comorbidity, DNA extraction, female, health care utilization, human, infant, male, methicillin resistant Staphylococcus aureus, molecular typing, multicenter study, nonhuman, nursing home patient, prevalence, scoring system, screening, Medical and Health Sciences, Epidemiology
Abstract

We assessed characteristics associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage among residents of 22 nursing homes. Of MRSA-positive swabs, 25% (208/824) were positive for CA-MRSA. Median facility CA-MRSA percentage was 22% (range, 0%-44%). In multivariate models, carriage was associated with age less than 65 years (odds ratio, 1.2; P

Published
2013

5. Differences in Methicillin-Resistant Staphylococcus aureus Strains Isolated from Pediatric and Adult Patients from Hospitals in a Large County in California

Author

Hudson, Lyndsey O, Murphy, Courtney R, Spratt, Brian G, Enright, Mark C, Terpstra, Leah, Gombosev, Adrijana, Hannah, Paul, Mikhail, Lydia, Alexander, Richard, Moore, Douglas F, and Huang, Susan S

Subjects
Clinical Research, Prevention, Emerging Infectious Diseases, Antimicrobial Resistance, Pediatric, Infectious Diseases, Age Factors, Aged, Aged, 80 and over, California, Child, Child, Preschool, Cluster Analysis, Cohort Studies, Community-Acquired Infections, Cross Infection, Female, Genotype, Hospitals, Humans, Infant, Male, Methicillin-Resistant Staphylococcus aureus, Middle Aged, Molecular Epidemiology, Molecular Typing, Prospective Studies, Staphylococcal Infections, adult, aged, article, bacterial strain, bacterium isolate, bacterium isolation, child, cohort analysis, controlled study, hospital patient, human, medicaid, methicillin resistant Staphylococcus aureus, nonhuman, preschool child, priority journal, prospective study, school child, United States, wound, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Microbiology
Abstract

Studies of U.S. epidemics of community- and health care-associated methicillin-resistant Staphylococcus aureus (MRSA) suggested differences in MRSA strains in adults and those in children. Comprehensive population-based studies exploring these differences are lacking. We conducted a prospective cohort study of inpatients in Orange County, CA, collecting clinical MRSA isolates from 30 of 31 Orange County hospitals, to characterize differences in MRSA strains isolated from children compared to those isolated from adults. All isolates were characterized by spa typing. We collected 1,124 MRSA isolates from adults and 159 from children. Annual Orange County population estimates of MRSA inpatient clinical cultures were 119/100,000 adults and 22/100,000 children. spa types t008, t242, and t002 accounted for 83% of all isolates. The distribution of these three spa types among adults was significantly different from that among children (χ(2) = 52.29; P < 0.001). Forty-one percent of adult isolates were of t008 (USA300), compared to 69% of pediatric isolates. In multivariate analyses, specimens from pediatric patients, wounds, non-intensive care unit (ICU) wards, and hospitals with a high proportion of Medicaid-insured patients were significantly associated with the detection of t008 strains. While community- and health care-associated MRSA reservoirs have begun to merge, significant differences remain in pediatric and adult patient populations. Community-associated MRSA spa type t008 is significantly more common in pediatric patients.

Published
2012

6. Complete Genomes of Two Clinical Staphylococcus aureus Strains: Evidence for the Rapid Evolution of Virulence and Drug Resistance

Author

Feil, Edward J., Lindsay, Jodi A., Peacock, Sharon J., Enright, Mark C., Foster, Tim J., Moore, Catrin E., Hurst, Laurence, Atkin, Rebecca, Barron, Andrew, Bason, Nathalie, Bentley, Stephen D., Chillingworth, Carol, Chillingworth, Tracey, Churcher, Carol, Clark, Louise, Corton, Craig, Cronin, Ann, Doggett, Jon, Dowd, Linda, Feltwell, Theresa, Hance, Zahra, Harris, Barbara, Hauser, Heidi, Holroyd, Simon, Jagels, Kay, James, Keith D., Lennard, Nicola, Line, Alexandra, Mayes, Rebecca, Moule, Sharon, Mungall, Karen, Ormond, Douglas, Quail, Michael A., Rabbinowitsch, Ester, Rutherford, Kim, Sanders, Mandy, Sharp, Sarah, Simmonds, Mark, Stevens, Kim, Whitehead, Sally, Barrell, Bart G., Spratt, Brian G., Parkhill, Julian, and Mekalanos, John J.

Published
2004

11. Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus

Author

McAdam, Paul R., Templeton, Kate E., Edwards, Giles F., Holden, Matthew T. G., Feil, Edward J., Aanensen, David M., Bargawi, Hiba J. A., Spratt, Brian G., Bentley, Stephen D., Parkhill, Julian, Enright, Mark C., Holmes, Anne, Girvan, E. Kirsty, Godfrey, Paul A., Feldgarden, Michael, Kearns, Angela M., Rambaut, Andrew, Robinson, D. Ashley, and Fitzgerald, J. Ross

Published
2012

13. A Population-Based Study of the Incidence and Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Disease in San Francisco, 2004—2005

Author

Liu, Catherine, Graber, Christopher J., Karr, Michael, Diep, Binh An, Basuino, Li, Schwartz, Brian S., Enright, Mark C., O'Hanlon, Simon J., Thomas, Jonathon C., Perdreau-Remington, Francoise, Gordon, Shelley, Gunthorpe, Helen, Jacobs, Richard, Jensen, Peter, Leoung, Giffford, Rumack, James S., and Chambers, Henry F.

Published
2008
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14. List of Contributors

Author

Abel-Santos, Ernesto, primary, Abraham, Soman N., additional, Aizawa, Shin-Ichi, additional, Aldape, Michael J., additional, Alexander, David C., additional, Allison, David G., additional, Amyes, Sebastian G.B., additional, Anderson, Burt E., additional, Anderson, Frank J., additional, Antelmann, Haike, additional, Austin, Frank W., additional, Ayllón, Nieves, additional, Bai, Fang, additional, Barbosa, Angela Silva, additional, Barer, Michael R., additional, Basarab, Gregory S., additional, Beaman, Blaine L., additional, Beard, Matthew, additional, Black, Carolyn M., additional, Blakely, Garry W., additional, Boiron, Patrick, additional, Bouabe, Hicham, additional, Bozue, Joel A., additional, Brinkman, Cassandra L., additional, Brubaker, Robert R., additional, Bryant, Amy E., additional, Cain, Robert J., additional, Calvo, Ana Cristina, additional, Carvalho, Eneas, additional, Capo, Christian, additional, Castillo-Ramirez, Santiago, additional, Chaddock, John A., additional, Chamberland, Robin R., additional, Clarridge, Jill E., additional, Cote, Christopher K., additional, Cox, Sarah L., additional, Cutler, Sally J., additional, Davidson, Donald J., additional, Day, Nicholas P.J., additional, de la Fuente, José, additional, De Jesus, Magdia, additional, Dorin, Julia R., additional, Dorman, Charles J., additional, Eakin, Ann E., additional, Egland, Paul G., additional, Ellis, Simon, additional, Enright, Mark C., additional, Evans, Benjamin A., additional, Everett, Jake A., additional, Falkinham, Joseph O., additional, Fan, Feinan, additional, Fan, Huizhou, additional, Faulds-Pain, Alexandra, additional, Feil, Edward J., additional, Figueroa, Cesar J., additional, Forsberg, Åke, additional, Foster, Timothy J., additional, Fox-Moon, Sandra M., additional, Fraga, Tatiana Rodrigues, additional, Fredricks, David N., additional, Freitag, Nancy E., additional, García-López, María-Luisa, additional, Garzetti, Debora, additional, Gemmell, Curtis G., additional, Geoghegan, Joan A., additional, Gillis, Thomas P., additional, Gilmore, Michael S., additional, Goldstone, Robert J., additional, Gray-Owen, Scott D., additional, Guiso, Nicole, additional, Hallstrom, Kelly N., additional, Harper, David R., additional, Harrington, Amanda T., additional, Harris, Jason B., additional, Hays, John P., additional, He, Yongqun, additional, Heffron, Jared D., additional, Heimer, Susan R., additional, High, Nicola J., additional, Hobot, Jan A., additional, Hultgren, Scott, additional, Humphreys, Tricia L., additional, Hunstad, David A., additional, Igietseme, Joseph U., additional, Inglis, Neil F., additional, Inglis, Tim J.J., additional, Isaac, Lourdes, additional, Janowicz, Diane M., additional, Jin, Shouguang, additional, Jin, Yongxin, additional, Johansson, Anna-Lena, additional, Johnston, Randal N., additional, Jones, Jessica L., additional, Justice, Sheryl S., additional, Kaakoush, Nadeem O., additional, Kalas, Vasilios, additional, Khare, Reeti, additional, Jordan, I. King, additional, Kobayashi, Keiko, additional, Kocan, Katherine M., additional, Könönen, Eija, additional, Kumar, Purnima S., additional, Lambert, Peter A., additional, Lamont, Richard J., additional, Lan, Ruiting, additional, Lang, Sue, additional, Lereclus, Didier, additional, Levett, Paul N., additional, Li, Xuefeng, additional, Liu, Dongyou, additional, Liu, Shu-Lin, additional, Ma, Lin, additional, Mahlen, Steven D., additional, Man, Si Ming, additional, Margolis, Elisa, additional, Marrie, Thomas J., additional, Martin, Melissa J., additional, Mayer, Leonard W., additional, McConville, Malcolm, additional, McCormick, Beth A., additional, McDowell, Andrew, additional, McHugh, Brian J., additional, McMullen, P. David, additional, McSheffrey, Gordon G., additional, Mege, Jean-Louis, additional, Merritt, Adam J., additional, Minnick, Michael F., additional, Mitchell, Hazel M., additional, Morrison, Donald, additional, Musser, Kimberlee A., additional, Nagahama, Masahiro, additional, Nagao, Prescilla Emy, additional, Nagy, István, additional, Salomonsson, Emelie Näslund, additional, Nazarian, Elizabeth J., additional, Nichols, Wright W., additional, Noppa, Laila, additional, Octavia, Sophie, additional, Oda, Masataka, additional, Ofek, Itzhak, additional, Oliver, James D., additional, Olson, Patrick D., additional, Omosun, Yusuf, additional, Ong, Edmund, additional, Osta, Rosario, additional, Otero, Andrés, additional, Oyston, Petra C.F., additional, Paris, Daniel H., additional, Patel, Robin, additional, Patrick, Sheila, additional, Pedra, Joao H.F., additional, Posteraro, Brunella, additional, Posteraro, Patrizia, additional, Poxton, Ian R., additional, Pujic, Petar, additional, Raffa, Brittany J., additional, Rakin, Alexander, additional, Ramarao, Nalini, additional, Ramirez, Mario, additional, Ravalison, Miora, additional, Reed, Kurt D., additional, Reglinski, Mark, additional, Richards, Allen L., additional, Riesbeck, Kristian, additional, Riley, Thomas V., additional, Rodríguez-Calleja, José-María, additional, Rodríguez-Nava, Verónica, additional, Rumbaugh, Kendra P., additional, Sanderson, Kenneth E., additional, Sanguinetti, Maurizio, additional, Santos, Jesús A., additional, Santos, Renato L., additional, Schaar, Viveka, additional, Scheld, W. Michael, additional, Schmitz, Jonathan E., additional, Schwartzman, Joseph D., additional, Severo, Maiara S., additional, Sharon, Nathan, additional, Shirtliff, Mark E., additional, Simner, Patricia J., additional, Šmajs, David, additional, Smith, David G.E., additional, Sorokin, Alexei, additional, Sprague, Lisa D., additional, Sriskandan, Shiranee, additional, Stevens, Dennis L., additional, Stratton, Charles W., additional, Strouhal, Michal, additional, Su, Yu Ching, additional, Sussman, Max, additional, Talbot, Elizabeth A., additional, Tang, Le, additional, Tang, Yi-Wei, additional, Taur, Ying, additional, Tessier, Jeffrey M., additional, Textoris, Julien, additional, Thirumalapura, Nagaraja R., additional, Tsuge, Hideaki, additional, Turenne, Christine Y., additional, Valvano, Miguel A., additional, Vázquez-Boland, José A., additional, Verhaegh, Suzanne J.C., additional, Volkan, Ender, additional, Vollmer, Waldemar, additional, Wade, William F., additional, Waites, Ken B., additional, Walker, Alan W., additional, Walker, David H., additional, Wang, Guiqing, additional, Wang, Qinning, additional, Wang, Xin, additional, Ward, Bruce, additional, Watson, Eleanor, additional, Weil, Ana A., additional, Welkos, Susan L., additional, Wen, Zhensong, additional, Wengenack, Nancy L., additional, Westblade, Lars F., additional, Wexler, Hannah M., additional, Wren, Brendan W., additional, Wu, Min, additional, Wu, Shangwei, additional, Wu, Weihui, additional, Xiao, Li, additional, Zhang, Jing-Ren, additional, Zhao, Zuotao, additional, and Zhong, Guangming, additional

Published
2015
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15. Antimicrobial Phages

Author

Harper, David R., primary, McConville, Malcolm, additional, Anderson, Frank J., additional, and Enright, Mark C., additional

Published
2015
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18. Characterisation of Bacteriophage-Encoded Depolymerases Selective for Key Klebsiella pneumoniae Capsular Exopolysaccharides

Author

Blundell-Hunter, George, primary, Enright, Mark C., additional, Negus, David, additional, Dorman, Matthew J., additional, Beecham, Gemma E., additional, Pickard, Derek J., additional, Wintachai, Phitchayapak, additional, Voravuthikunchai, Supayang P., additional, Thomson, Nicholas R., additional, and Taylor, Peter W., additional

Published
2021
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20. Global distribution of Panton-Valentine leukocidin--positive methicillin-resistant Staphylococcus aureus, 2006

Author

Tristan, Anne, Bes, Michele, Meugnier, Helene, Lina, Gerard, Bozdogan, Bulent, Courvalin, Patrice, Reverdy, Marie-Elisabeth, Enright, Mark C., Vandenesch, Francois, and Etienne, Jerome

Subjects
Drug resistance -- Research, Staphylococcus aureus -- Genetic aspects, Staphylococcus aureus -- Development and progression, Staphylococcus aureus -- Prevention
Abstract

We determined the agr type, multilocus sequence type, protein A gene type (spa typing), toxin gene profile, and antimicrobial drug resistance profile of 469 isolates of Panton-Valentine leukocidin--positive community-acquired methicillin-resistant [...]

Published
2007

21. Evolutionary genetics of the accessory gene regulator (agr) locus in Staphylococcus aureus

Author

Robinson, D. Ashley, Monk, Alastair B., Cooper, Jessica E., Feil, Edward J., and Enright, Mark C.

Subjects
Staphylococcus aureus -- Genetic aspects, Staphylococcus aureus -- Research, Gene expression -- Research, Phylogeny -- Analysis, Biological sciences
Abstract

The accessory gene regulator (agr) locus influences the expression of many virulence genes in the human pathogen Staphylococcus aureus. Four allelic groups of agr, which generally inhibit the regulatory activity of each other, have been identified within the species. Interference in virulence gene expression caused by different agr groups has been suggested to be a mechanism for isolating bacterial populations and a fundamental basis for subdividing the species. To test the hypothesis that the species is phylogenetically structured according to agr groups, we mapped agr groups onto a clone phylogeny inferred from partial sequences of 14 genes from 27 genetically diverse strains. Shimodaira-Hasegawa and parametric bootstrap tests rejected the hypotheses that the species is subdivided into three or five monophyletic agr groups but failed to reject the hypothesis that the species is subdivided into two groups that each consist of multiple clonal complexes and multiple agr groups. Additional evidence for agr recombination is found from clustered polymorphisms in complete agr sequences. However, agr recombination has not occurred frequently or randomly through time, because the topology and branch lengths of the clone phylogeny are reflected within each agr group. To account for these observations, we propose a new evolutionary model that involves a genetically polymorphic ancestral population of S. aureus that horizontally transferred agr groups between two subspecies groups near the time that these subspecies groups diverged.

Published
2005

22. Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance

Author

Holden, Matthew T.G., Feil, Edward J., Lindsay, Jodi A., Peacock, Sharon J., Day, Nicholas P.J., Enright, Mark C., Foster, Tim J., Moore, Catrin E., Hurst, Laurence, Atkin, Rebecca, Barron, Andrew, Bason, Nathalie, Bentley, Stephen D., Chillingworth, Carol, Chillingworth, Tracey, Churcher, Carol, Clark, Louise, Corton, Craig, Cronin, Ann, Doggett, Jon, Dowd, Linda, Feltwell, Theresa, Hance, Zahra, Harris, Barbara C., Bishop, Hauser, Heidi, Holroyd, Simon, Jagels, Kay, James, Keith D., Lennard, Nicola, Line, Alexandra, Mayes, Rebecca, Moule, Sharon, Mungall, Karen, Ormond, Douglas, Quail, Michael A., Rabbinowitsch, Ester, Rutherford, Kim, Sanders, Mandy, Sharp, Sarah, Simmonds, Mark, Stevens, Kim, Whitehead, Sally, Barrell, Bart G., Spratt, Brian G., and Parkhill, Julian

Subjects
Drug resistance in microorganisms -- Research, Staphylococcus aureus -- Research, Staphylococcus aureus -- Genetic aspects, Science and technology, National Academy of Sciences -- Research
Abstract

Staphylococcus aureus is an important nosocomial and community-acquired pathogen. Its genetic plasticity has facilitated the evolution of many virulent and drug-resistant strains, presenting a major and constantly changing clinical challenge. We sequenced the [approximately equal to] 2.8-Mbp genomes of two disease-causing S. aureus strains isolated from distinct clinical settings: a recent hospital-acquired representative of the epidemic methicillin-resistant S. aureus EMRSA-16 clone (MRSA252), a clinically important and globally prevalent lineage; and a representative of an invasive community-acquired methicillin-susceptible S. aureus clone (MSSA476). A comparative-genomics approach was used to explore the mechanisms of evolution of clinically important S, aureus genomes and to identify regions affecting virulence and drug resistance. The genome sequences of MRSA252 and MSSA476 have a well conserved core region but differ markedly in their accessory genetic elements. MRSA252 is the most genetically diverse S. aureus strain sequenced to date: [approximately equal to] 6% of the genome is novel compared with other published genomes, and it contains several unique genetic elements. MSSA476 is methicillin-susceptible, but it contains a novel Staphylococcal chromosomal cassette (SCC) mec-like element (designated SC[C.sub.476]), which is integrated at the same site on the chromosome as SCCmec elements in MRSA strains but encodes a putative fusidic acid resistance protein. The crucial role that accessory elements play in the rapid evolution of S. aureus is clearly illustrated by comparing the MSSA476 genome with that of an extremely closely related MRSA community-acquired strain; the differential distribution of large mobile elements carrying virulence and drug-resistance determinants may be responsible for the clinically important phenotypic differences in these strains.

Published
2004

23. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. (Research)

Author

Vandenesch, Francois, Naimi, Timothy, Enright, Mark C., Lina, Gerard, Nimmo, Graeme R., Heffernan, Helen, Liassine, Nadia, Bes, Michele, Greenland, Timothy, Reverdy, Marie-Elisabeth, and Etienne, Jerome

Subjects
Staphylococcal infections -- Research
Abstract

Infections caused by community-acquired (CA)-methicillin-resistant Staphylococcus aureus (MRSA) have been reported worldwide. We assessed whether any common genetic markers existed among 117 CA-MRSA isolates from the United States, France, Switzerland, [...]

Published
2003

24. How clonal is Staphylococcus aureus?

Author

Feil, Edward J., Cooper, Jessica E., Grundmann, Hajo, Robinson, D. Ashley, Enright, Mark C., Berendt, Tony, Peacock, Sharon J., Smith, John Maynard, Murphy, Michael, Spratt, Brian G., Moore, Catrin E., and Day, Nicholas P.J.

Subjects
Microbial populations -- Genetic aspects, Cloning -- Genetic aspects, Staphylococcus -- Psychological aspects, Staphylococcus -- Genetic aspects, Bacteriology -- Research, Biological sciences
Abstract

Staphylococcus aureus is an important human pathogen and represents a growing public health burden owing to the emergence and spread of antibiotic-resistant clones, particularly within the hospital environment. Despite this, basic questions about the evolution and population biology of the species, particularly with regard to the extent and impact of homologous recombination, remain unanswered. We address these issues through an analysis of sequence data obtained from the characterization by multilocus sequence typing (MLST) of 334 isolates of S. aureus, recovered from a well-defined population, over a limited time span. We find no significant differences in the distribution of multilocus genotypes between strains isolated from carriers and those from patients with invasive disease; there is, therefore, no evidence from MLST data, which index variation within the stable 'core' genome, for the existence of hypervirulent clones of this pathogen. Examination of the sequence changes at MLST loci during clonal diversification shows that point mutations give rise to new alleles at least 15-fold more frequently than does recombination. This contrasts with the naturally transformable species Neisseria meningitidis and Streptococcus pneumoniae, in which alleles change between 5- and 10-fold more frequently by recombination than by mutation. However, phylogenetic analysis suggests that homologous recombination does contribute toward the evolution of this species over the long term. Finally, we note a striking excess of nonsynonymous substitutions in comparisons between isolates belonging to the same clonal complex compared to isolates belonging to different clonal complexes, suggesting that the removal of deleterious mutations by purifying selection may be relatively slow.

Published
2003

26. Contributors

Author

Alangaden, George J., primary, Aldape, Michael J., additional, Allardet-Servent, Jérôme, additional, Allen, Upton D., additional, Ammerlaan, Heidi S.M., additional, Angelakis, Emmanouil, additional, Artenstein, Andrew, additional, Asboe, David, additional, Asiedu, Kingsley B., additional, Atherton, John C., additional, Aw, Tar-Ching, additional, Baid-Agrawal, Seema, additional, Bailey, Robin, additional, Bandel, Christopher, additional, Barie, Philip S., additional, Barillo, David J., additional, Bart, Pierre-Alexandre, additional, Bayston, Roger, additional, Beard, C. Ben, additional, Beeching, Nick J., additional, Bégué, Rodolfo E., additional, Benhamou, Yves, additional, Benson, Constance A., additional, Berbari, Elie F., additional, Berendt, Anthony R., additional, Bhatta, Madhav P., additional, Bille, Jacques, additional, Bitnun, Ari, additional, Black, Finn T., additional, Blair, Iain, additional, Blanche, Stéphane, additional, Bleck, Thomas P., additional, Bleeker-Rovers, Chantal P., additional, Bleijenberg, Gijs, additional, Bloch, Karen C., additional, Bonten, Marc J.M., additional, Boucher, Charles A.B., additional, Bourayou, Rafik, additional, Bouza, Emilio S., additional, Bowie, William R., additional, Brause, Barry D., additional, Brisse, Sylvain, additional, Britton, Warwick, additional, Brook, Itzhak, additional, Brown, David W.G., additional, Brun-Buisson, Christian, additional, Brust, James C.M., additional, Bryant, Amy E., additional, Bryskier, André, additional, Buller, R. Mark L, additional, Bush, Karen, additional, Calandra, Thierry, additional, Cameron, D. William, additional, Caraël, Michel, additional, Carr, Michael J., additional, Casas, Inmaculada, additional, Chambers, Stephen T., additional, Chiller, Katarina G., additional, Chiller, Tom M., additional, Chiodini, Peter L., additional, Chopra, Ian, additional, Chu, Anthony C., additional, Chung, Kevin K., additional, Clark, Benjamin M., additional, Clumeck, Nathan, additional, Cockerell, Clay J., additional, Cohen, Jonathan, additional, Collinge, John, additional, Conlon, Christopher P., additional, Corey, G. Ralph, additional, Cross, Alan, additional, Cross, John H., additional, Currier, Judith, additional, Curtis, Carmel M., additional, Dallabetta, Gina, additional, Davidson, Robert N., additional, Davies, Jane, additional, Day, Jeremy, additional, Day, Nicholas P.J., additional, De Gascun, Cillian F., additional, de Wit, Stéphane, additional, Delmont, Jean, additional, Dennis, David T., additional, Diemert, David J., additional, Doganay, Mehmet, additional, Doherty, Tom, additional, Dolecek, Christiane, additional, Donati, Stéphane Y., additional, Dondorp, Arjen M., additional, Doudier, Barbara, additional, Drancourt, Michel, additional, Drekonja, Dimitri M., additional, Drew, Richard H., additional, Duker, Jay S., additional, Dummer, J. Stephen, additional, Edwards, Charles N., additional, Ekkelenkamp, Miquel B., additional, Enright, Mark C., additional, Epstein, Paul R., additional, Erard, Veronique, additional, Eziefula, Alice Chijioke, additional, Feinberg, Mark B., additional, Fenollar, Florence, additional, Fenwick, Alan, additional, Fernandez, Luis, additional, Fierer, Joshua, additional, Finch, Roger G., additional, Flexner, Charles W., additional, Fluit, Ad C., additional, Ford-Jones, Elizabeth Lee, additional, Fournier, Pierre-Edouard, additional, Fraser, Victoria, additional, French, Martyn A., additional, Friedland, Jon S., additional, Fritz, Joseph M., additional, Furuya, E. Yoko, additional, Gage, Kenneth L., additional, Garcia, Lynne S., additional, Gastañaduy, Arturo S., additional, Ghanem, Khalil G., additional, Giannella, Maddalena, additional, Glaser, Carol A., additional, Glesby, Marshall J., additional, Glover, Sarah, additional, Glupczynski, Youri, additional, Gnann, John W., additional, Goddard, Andrew F., additional, Goldstein, Ellie J.C., additional, González, Iveth J., additional, Gorbach, Sherwood L., additional, Gottstein, Bruno, additional, Gowda, Ravi, additional, Grabenstein, John D., additional, Grange, John M., additional, Green, Michael D., additional, Green, Stephen T., additional, Greenblatt, Danielle T., additional, Greenwood, Brian, additional, Gregson, Aric L., additional, Groll, Andreas H., additional, Gupta, Aditya K., additional, Gwee, Kok-Ann, additional, Hall, William, additional, Hammer, Scott M., additional, Handa, Sajeev, additional, Hanfelt-Goade, Diane, additional, Harari, Alexandre, additional, Harris, Marianne, additional, Hartman, Barry J., additional, Hay, Roderick J., additional, Henderson, David K., additional, Hensley, Lisa E., additional, Herbert, Luke, additional, Hill, David R., additional, Hills, Timothy J., additional, Hinze, John David, additional, Hirsch, Hans H., additional, Hirschel, Bernard, additional, Hoepelman, Andy I.M., additional, Holland, Steven M., additional, Horgan, Mary M., additional, Howe, Robin, additional, Hughes, James M., additional, Hull, Mark W., additional, Inderlied, Clark B., additional, Ison, Michael G., additional, Jenks, Peter J., additional, Johnson, James R., additional, Jones, Theodore, additional, Kanno, Mettassebia, additional, Kauffman, Carol, additional, Kelly, Patrick, additional, Kendler, Jason S., additional, Keynan, Yoav, additional, Khan, Ali S., additional, Kho, Grace T., additional, Kinghorn, George R., additional, Klapper, Paul E., additional, Kluytmans, Jan AJW, additional, Kok, Menno, additional, Koné-Paut, Isabelle, additional, Krieger, John N., additional, Kroes, Aloys C.M., additional, Kroon, Frank P., additional, Kubin, Christine J., additional, La Rosa, Alberto M., additional, Lalani, Tahaniyat, additional, Lalloo, David G., additional, Lambert, Harold, additional, Landraud, Luce, additional, Lawn, Stephen D., additional, Pharm, Phillipe Lehours, additional, Leone, Marc, additional, Levi, Itzchak, additional, Levitt, Alexandra M., additional, Lindquist, H. D. Alan, additional, Lloyd, Graham, additional, Looney, David J., additional, Lowy, Franklin D., additional, Luft, Benjamin J., additional, Lynn, William A., additional, Macielag, Mark J., additional, Mackowiak, Philip A., additional, MacPherson, Paul A., additional, Maghraoui-Slim, Valérie, additional, Main, Janice, additional, Mallet, Vincent, additional, Mangino, Julie E., additional, Manuel, Oriol, additional, Marchetti, Oscar, additional, Marks, Kristen, additional, Marr, Kieren A., additional, Martin, Claude, additional, Martín-Rabadán, Pablo, additional, Martinez, Augusto Julio, additional, Mascini, Ellen M., additional, Mayer, Kenneth H., additional, McCormick, Joseph B., additional, McGready, Rose, additional, McKendrick, Michael W., additional, Mead, Simon, additional, Mégraud, Francis, additional, Meheus, André Z., additional, Meintjes, Graeme, additional, Michaels, Marian G., additional, Miles, Michael, additional, Miller, Alastair, additional, Mimiaga, Matthew J., additional, Mingeot-Leclercq, Marie-Paule, additional, Mitchell, Thomas G., additional, Moise, Pamela A., additional, Montaner, Julio, additional, Moore, Caroline B., additional, Moreillon, Philippe, additional, Morgan-Capner, Peter, additional, Montessori, Valentina, additional, Moss, Peter, additional, Muñoz, Patricia, additional, Naber, Kurt G., additional, Nakhla, Sammy, additional, Narain, Jai P., additional, Nathwani, Dilip, additional, Newton, Paul, additional, Nguyen, Chinh, additional, Nicolle, Lindsay E., additional, Niederman, Michael S., additional, Noel, Gary J., additional, Norrby, S. Ragnar, additional, Nosten, François, additional, Notarangelo, Luigi Daniele, additional, Nyirjesy, Paul, additional, O'Connell, P. Ronan, additional, Odorico, Jon S., additional, Ong, Edmund L.C., additional, Opal, Steven M., additional, Ormerod, L. Peter, additional, Osmon, Douglas R., additional, Ottesen, Eric A., additional, Palacios, Gustavo, additional, Pantaleo, Giuseppe, additional, Papazian, Laurent, additional, Parola, Philippe, additional, Pascual, Manuel A., additional, Patrozou, Eleni, additional, Paya, Carlos, additional, Peacock, Sharon J., additional, Pechère, Jean-Claude, additional, Perkins, Mark D., additional, Peters, Barry, additional, Pfyffer, Gaby E., additional, Pham, Paul A., additional, Piot, Peter, additional, Placko-Parola, Geraldine, additional, Pol, Stainslas, additional, Posfay-Barbe, Klara M., additional, Powderly, William G., additional, Pozniak, Anton, additional, Prod'hom, Guy, additional, Quinn, Thomas C., additional, Rahn, Daniel W., additional, Rana, Aadia I., additional, Raoult, Didier, additional, Raz, Raul, additional, Razonable, Raymund, additional, Read, Robert C., additional, Reynolds, Stephen J., additional, Richardson, Malcolm D., additional, Robinson, Christopher C., additional, Rooijakkers, Suzan H.M., additional, Rosenbluth, Daniel, additional, Rosenzweig, Sergio D., additional, Rovery, Clarisse, additional, Rubin, Robert H., additional, Rubinovitch, Bina, additional, Rubins, Kathleen H., additional, Rubinstein, Ethan, additional, Ryan, Greg, additional, Ryder, Stephen, additional, Safren, Steven, additional, Sahasrabuddhe, Vikrant V., additional, Saikku, Pekka A.I., additional, Sakoulas, George, additional, Salazar, Juan Carlos, additional, Salvaggio, Michelle R., additional, Schaffer, Kirsten, additional, Schmitz, Franz-Josef, additional, Schooley, Robert T., additional, Schumacher, Richard-Fabian, additional, Scrimgeour, Euan M., additional, Seddon, James, additional, Seifert, Harald, additional, Serjeant, Graham R., additional, Sha, Beverly E., additional, Shah, Keerti V., additional, Shapiro, Daniel S., additional, Sheehan, Gerard, additional, Shoham, Shmuel, additional, Simmons, Cameron P., additional, Simonsen, Kari A., additional, Singh, Neeraj, additional, Slack, Mary P.E., additional, Sobel, Jack D., additional, Sopirala, Madhuri M., additional, Spacek, Lisa A., additional, Sriskandan, Shiranee, additional, Stanley, Samuel L., additional, Steckelberg, James M., additional, Stephenson, Iain, additional, Stevens, Dennis L., additional, Straus, Walter L., additional, Sturm, Willem, additional, Summerbell, Richard C., additional, Susa, Joseph S., additional, Tabrizi, Sarah J., additional, Tack, Marc A., additional, Taplitz, Randy, additional, Tebas, Pablo, additional, Temmerman, Marleen, additional, Thijsen, Steven F.T., additional, Thomas, Lora D., additional, Thomson, Gail, additional, Thwaites, Guy E., additional, Tirelli, Umberto, additional, Tolkoff-Rubin, Nina E., additional, Tønjum, Tone, additional, Torriani, Francesca J., additional, Townsend, Gregory C., additional, Masó, Gloria Trallero, additional, Tulkens, Paul M., additional, Tunkel, Allan R., additional, Vaccher, Emanuela, additional, Vallet-Pichard, Anaïs, additional, Van Bambeke, Françoise, additional, van de Beek, Diederik, additional, van der Meer, Jos W.M., additional, van Loon, Anton M., additional, van Putten, Jos, additional, Vaudaux, Bernard P., additional, Vermund, Sten H., additional, Verstraelen, Hans, additional, Verweij, Paul, additional, Viscidi, Raphael P., additional, Visvanathan, Kumar, additional, Visvesvara, Govinda S., additional, von Seidlein, Lorenz, additional, Wagenlehner, Florian M.E., additional, Wahl-Jensen, Victoria, additional, Walsh, Thomas J., additional, Warhurst, David C., additional, Warnock, David W., additional, Warrell, David A., additional, Warrell, Mary J., additional, Warris, Adilia, additional, Weber, Rainer, additional, Weidner, Wolfgang, additional, Weston, Vivienne C., additional, Whimbey, Estella, additional, Whitby, Michael, additional, White, Peter J., additional, Whitty, Christopher J.M., additional, Willems, Rob J.L., additional, Williams, Emrys, additional, Wilson, Cara, additional, Wilson, Mary E., additional, Winn, Richard E., additional, Winthrop, Kevin L., additional, Wiselka, Martin J., additional, Wisplinghoff, Hilmar, additional, Wolfe, Cameron R., additional, Wood, Robin, additional, Wright, Natalie, additional, Yankaskas, James R., additional, Zaidi, Najam A., additional, Zenilman, Jonathan M., additional, Zhang, Yaobi, additional, Zuckerman, Arie J., additional, Zuckerman, Jane Nicola, additional, and Zumla, Alimuddin, additional

Published
2010
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27. Rapid Whole-Genome Sequencing for Investigation of a Neonatal MRSA Outbreak

Author

Köser, Claudio U., Holden, Matthew T.G., Ellington, Matthew J., Cartwright, Edward J.P., Brown, Nicholas M., Ogilvy-Stuart, Amanda L., Hsu, Li Yang, Chewapreecha, Claire, Croucher, Nicholas J., Harris, Simon R., Sanders, Mandy, Enright, Mark C., Dougan, Gordon, Bentley, Stephen D., Parkhill, Julian, Fraser, Louise J., Betley, Jason R., Schulz-Trieglaff, Ole B., Smith, Geoffrey P., and Peacock, Sharon J.

Published
2012
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30. Serotype 14 variants of the Spanish penicillin-resistant serotype 9V clone of Streptococcus pneumoniae arose by large recombinational replacements of the cpsA-pbp1a region

Author

Coffey, Tracey J., Daniels, Margaret, Enright, Mark C., and Spratt, Brian G.

Subjects
Streptococcus pneumoniae -- Genetic aspects, Drug resistance in microorganisms -- Genetic aspects, Penicillin -- Research, Genetic recombination -- Research, Biological sciences
Abstract

Research was conducted to examine the serotype 14 variants of the Spanish penicillin-resistant serotype 9V clone of Streptococcus pneumoniae which have resulted from large recombinational replacements of the cpsA-pbp1a region. The relationship of the penicillin-resistant serotype 14 isolates to other penicillin-resistant pneumococci was established via multilocus sequence typing and were demonstrated to be serotype variants of the MPSp9V. The molecular basis of the emergence of the variants was elucidated through an analysis of their capsular locus and flanking regions.

Published
1999

39. Vancomycin susceptibility within methicillin-resistant Staphylococcus aureus lineages

Author

Howe, Robin A., Monk, Alastair, Wootton, Mandy, Walsh, Timothy R., and Enright, Mark C.

Subjects
Vancomycin -- Research, Staphylococcus -- Research
Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) with reduced vancomycin susceptibility vancomycin-intermediate S. aureus (VISA) has been reported from many countries. Whether resistance is evolving regularly in different genetic backgrounds or in a [...]

Published
2004

41. Further understanding of 's ability to horizontally acquire virulence: possible intervention strategies.

Author

Redfern, James and Enright, Mark C.

Subjects
GENETICS, ANIMAL experimentation, CELL physiology, PSEUDOMONAS diseases, PSEUDOMONAS, MICROBIAL virulence, DRUG resistance in microorganisms, ANTIBIOTICS, PHARMACODYNAMICS
Abstract

Introduction: Pseudomonas aeruginosa is a common, ubiquitous bacterium that is found in natural environments but is also a successful opportunistic pathogen of humans and plants. The reasons for this flexibility and evolutionary success can be attributed to its ability to readily acquire new genes to ensure its survival enabling it to survive desiccation, the action of antimicrobial compounds and invade new territories such as modern hospitals with high levels of antibiotic usage.Areas covered: Literature was searched using PubMed and Web of science (05/19 to 05/20). Identified studies paint a picture of a dynamic, highly variable population shaped by frequent intra- and inter-species horizontal gene transfer resulting in a species able to resist the action of antibiotics and deploy multiple virulence strategies controlled by complex quorum-sensing systems. We investigate possible control measures including anti-virulence and environmental control measures.Expert opinion: P.aeruginosa is a resilient, richly diverse species but also a global health threat due to the emergence and global dissemination of successful multiresistant clones that resist all antibiotics. Genomics offers the potential for rapid identification of 'high-risk' clones to guide chemotherapy, but novel control measures are also required to slow the species progression to pan-resistance. [ABSTRACT FROM AUTHOR]

Published
2020
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42. Retraction

Author

Moore, Catrin E., Enright, Mark C., Berendt, Anthony R., Smith, John Maynard, Murphy, Michael F., Peacock, Sharon J., Spratt, Brian G., and Feil, Edward J.

Published
2002

44. A novel bacteriophage cocktail reduces and disperses Pseudomonas aeruginosa biofilms under static and flow conditions

Author

Alves, Diana R., Perez‐Esteban, P., Kot, W., Bean, J.E., Arnot, T., Hansen, L.H., Enright, Mark C., and Jenkins, A. Tobias A.

Subjects
Biofilms, Pseudomonas aeruginosa, Humans, Bacteriophages, Pseudomonas Infections, biochemical phenomena, metabolism, and nutrition, Research Articles, Research Article
Abstract

Summary P seudomonas aeruginosa is an opportunistic human pathogen that forms highly stable communities – biofilms, which contribute to the establishment and maintenance of infections. The biofilm state and intrinsic/acquired bacterial resistance mechanisms contribute to resistance/tolerance to antibiotics that is frequently observed in P . aeruginosa isolates. Here we describe the isolation and characterization of six novel lytic bacteriophages: viruses that infect bacteria, which together efficiently infect and kill a wide range of P . aeruginosa clinical isolates. The phages were used to formulate a cocktail with the potential to eliminate P . aeruginosa PAO1 planktonic cultures. Two biofilm models were studied, one static and one dynamic, and the phage cocktail was assessed for its ability to reduce and disperse the biofilm biomass. For the static model, after 4 h of contact with the phage suspension (MOI 10) more than 95% of biofilm biomass was eliminated. In the flow biofilm model, a slower rate of activity by the phage was observed, but 48 h after addition of the phage cocktail the biofilm was dispersed, with most cells eliminated (> 4 logs) comparing with the control. This cocktail has the potential for development as a therapeutic to control P . aeruginosa infections, which are predominantly biofilm centred.

Published
2016

45. CRISPR-Cas Systems Impact Pseudomonas aeruginosa Genome Structure

Author

LaFave, Matthew C., Belkum, Alex Van, Soriaga, Leah B., Srividya Akella, E. Magda Barbu, Hannum, Gregory, Miller, Kristofer, Enright, Mark C., Brami, Daniel, Felderman, Martina, Schwartz, Ariel, Richardson, Toby H., Peterson, Todd C., Bolyn Hubby, and Cady, Kyle C.

Abstract

Pseudomonas aeruginosa is both an antibiotic-resistant opportunistic pathogen and an important model of type I clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated protein (CRISPR-Cas) systems. Comparative genomics has identified several CRISPR-Cas subtypes, and it was previously unclear how these immune modules might influence the genome content of P. aeruginosa. To better understand the distribution of CRISPR-Cas subtypes and their impact on genome composition, we annotated 672 P. aeruginosa clinical isolates. We found that CRISPR-Cas systems modulate genome size and accessory elements. In addition, we identified a novel, putatively mobile type I-C CRISPR-Cas system. In the process, we also created a global spacer library that provides a new means of identifying accessory fragments, and facilitates CRISPR typing of many P. aeruginosa strains. Finally, we have made the assemblies of 282 newly-sequenced P. aeruginosa isolates public as an NCBI BioProject (ID: PRJNA297679).

Published
2016
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47. Estimating Recombinational Parameters in Streptococcus pneumoniae From Multilocus Sequence Typing Data

Author

Feil, Edward J., Smith, John Maynard, Enright, Mark C., and Spratt, Brian G.

Subjects
Streptococcus pneumoniae -- Research, Human genetics -- Research, Biological sciences
Abstract

Multilocus sequence typing (MLST) is a highly discriminatory molecular typing method that defines isolates of bacterial pathogens using the sequences of ~450-bp internal fragments of seven housekeeping genes. This technique has been applied to 575 isolates of Streptococcus pneumoniae and identifies a number of discrete clonal complexes. These clonal complexes are typically represented by a single group of isolates sharing identical alleles at all seven loci, plus single-locus variants that differ from this group at only one out of the seven loci. As MLST is highly discriminatory, the members of each clonal complex can be assumed to have a recent common ancestor, and the molecular events that give rise to the single-locus variants can be used to estimate the relative contributions of recombination and mutation to clonal divergence. By comparing the sequences of the variant alleles within each clonal complex with the allele typically found within that clonal complex, we estimate that recombination has generated new alleles at a frequency ~10-fold higher than mutation, and that a single nucleotide site is ~50 times more likely to change through recombination than mutation. We also demonstrate how to estimate the average length of recombinational replacements from MLST data.

Published
2000

48. Enhancement of the antimicrobial properties of bacteriophage-K via stabilisation using oil-in-water nano-emulsions

Author

Perez Esteban, Patricia, Alves, Diana R., Enright, Mark C., Bean, Jessica E., Gaudion, Alison, Jenkins, A. T A, Young, Amber E R, and Arnot, Tom C.

Subjects
oil-in-water nano-emulsion, burn wound related infections, responsive wound dressings, Phage therapy, S. aureus infections
Abstract

Bacteriophage therapy is a promising new treatment that may help overcome the threat posed by antibiotic-resistant pathogenic bacteria, which are increasingly identified in hospitalised patients. The development of biocompatible and sustainable vehicles for incorporation of viable bacterial viruses into a wound dressing is a promising alternative. This paper evaluates the anti-microbial efficacy of Bacteriophage K against Staphylococcus aureus over time, when stabilised and delivered via an oil-in-water nano-emulsion. Nano-emulsions were formulated via thermal phase inversion emulsification, and then bacterial growth was challenged with either native emulsion, or emulsion combined with Bacteriophage K. Bacteriophage infectivity, and the influence of storage time of the preparation, were assessed by turbidity measurements of bacterial samples. Newly prepared Bacteriophage K / nano-emulsion formulations have greater anti-microbial activity than freely suspended bacteriophage. The phage loaded emulsions caused rapid and complete bacterial death of three different strains of Staphylococcus aureus. The same effect was observed for preparations that were either stored at room temperature (18 - 20°C), or chilled at 4°C, for up to 10 days of storage. A response surface design of experiments was used to gain insight on the relative effects of the emulsion formulation on bacterial growth and phage lytic activity. More diluted emulsions had a less significant effect on bacterial growth, and diluted bacteriophage-emulsion preparations yielded greater antibacterial activity. The enhancement of bacteriophage activity when delivered via nano-emulsions has yet to be reported. This prompts further investigation into the use of these formulations for the development of novel anti-microbial wound management strategies.

Published
2014

49. An essential role for the baseplate protein Gp45 in phage adsorption to Staphylococcus aureus

Author

Li, Xuehua, primary, Koç, Cengiz, additional, Kühner, Petra, additional, Stierhof, York-Dieter, additional, Krismer, Bernhard, additional, Enright, Mark C., additional, Penadés, José R., additional, Wolz, Christiane, additional, Stehle, Thilo, additional, Cambillau, Christian, additional, Peschel, Andreas, additional, and Xia, Guoqing, additional

Published
2016
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50. Phylogenetic Distribution of CRISPR-Cas Systems in Antibiotic-Resistant Pseudomonas aeruginosa

Author

van Belkum, Alex, primary, Soriaga, Leah B., additional, LaFave, Matthew C., additional, Akella, Srividya, additional, Veyrieras, Jean-Baptiste, additional, Barbu, E. Magda, additional, Shortridge, Dee, additional, Blanc, Bernadette, additional, Hannum, Gregory, additional, Zambardi, Gilles, additional, Miller, Kristofer, additional, Enright, Mark C., additional, Mugnier, Nathalie, additional, Brami, Daniel, additional, Schicklin, Stéphane, additional, Felderman, Martina, additional, Schwartz, Ariel S., additional, Richardson, Toby H., additional, Peterson, Todd C., additional, Hubby, Bolyn, additional, and Cady, Kyle C., additional

Published
2015
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