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Copyright of Journal of Zhejiang University: Science B is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Multidrug efflux pumps are protein complexes located in the cell envelope that enable bacteria to expel, not only antibiotics, but also a wide array of molecules relevant for infection. Hence, they are important players in microbial pathogenesis. On the one hand, efflux pumps can extrude exogenous compounds, including host-produced antimicrobial molecules. Through this extrusion, pathogens can resist antimicrobial agents and evade host defenses. On the other hand, efflux pumps also have a role in the extrusion of endogenous compounds, such as bacterial intercommunication signaling molecules, virulence factors or metabolites. Therefore, efflux pumps are involved in the modulation of bacterial behavior and virulence, as well as in the maintenance of the bacterial homeostasis under different stresses found within the host. This review delves into the multifaceted roles that efflux pumps have, shedding light on their impact on bacterial virulence and their contribution to bacterial infection. These observations suggest that strategies targeting bacterial efflux pumps could both reinvigorate the efficacy of existing antibiotics and modulate the bacterial pathogenicity to the host. Thus, a comprehensive understanding of bacterial efflux pumps can be pivotal for the development of new effective strategies for the management of infectious diseases. [ABSTRACT FROM AUTHOR]

Bacteria utilize small signal molecules to monitor population densities. Bacteria arrange gene regulation in a method called Quorum Sensing (QS). The most widespread signalling molecules are N-Acyl Homoserine Lactones (AHLs/HSLs) for Gram-negative bacteria communities. QS plays significant role in the organizing of the bacterial gene that adapts to harsh environmental conditions for bacteria. It is involved in the arrangement of duties, such as biofilm formation occurrence, virulence activity of bacteria, production of antibiotics, plasmid conjugal transfer incident, pigmentation phenomenon and production of exopolysaccharide (EPS). QS obviously impacts on human health, agriculture and environment. AHL-related QS researches have been extensively studied and understood in depth for cell to cell intercommunication channel in Gram-negative bacteria. It is understood that AHL-based QS research has been extensively studied for cell-to-cell communication in Gram-negative bacteria; hence, a comprehensive study of AHLs, which are bacterial signal molecules, is required. The purpose of this review is to examine the effects of QS-mediated AHLs in many areas by looking at them from a different perspectives, such as clinic samples, food industry, aquatic life and wastewater treatment system. [ABSTRACT FROM AUTHOR]

Antibiotics play a key role in the prevention and treatment of bacterial diseases for human and animals. The widespread use of antibiotics results in bacterial exposure to the concentrations that are lower than the MIC (that is, sub-inhibitory concentration (sub-MIC)) in the environment, humans, and livestock, which can lead to antibiotic resistance. In this review, we focus on the impact of sub-MIC antibiotics in bacterial virulence. This paper summarized the known relationships between sub-MIC antibiotics in the environment and bacterial virulence. Together, considering the impact of sub-MIC antibiotics and their alternative products in the virulence of bacteria, it is helpful to the rational use of antibiotics and the development of antibiotic alternative products to provide new insights. Key points • Sub-MIC level antibiotics exist in the environment, humans, and livestock. • The review includes mechanisms of sub-MIC antibiotics in bacterial virulence. • New antibacterial strategies and agents are being a new way to weaken virulence. [ABSTRACT FROM AUTHOR]

Pseudomonas syringae pv. tabaci 6605 (Pta6605) is a causal agent of wildfire disease in host tobacco plants and is highly motile. Pta6605 has multiple clusters of chemotaxis genes including cheA, a gene encoding a histidine kinase, cheY, a gene encoding a response regulator, mcp, a gene for a methyl-accepting chemotaxis protein, as well as flagellar and pili biogenesis genes. However, only two major chemotaxis gene clusters, cluster I and cluster II, possess cheA and cheY. Deletion mutants of cheA or cheY were constructed to evaluate their possible role in Pta6605 chemotaxis and virulence. Motility tests and a chemotaxis assay to known attractant demonstrated that cheA2 and cheY2 mutants were unable to swarm and to perform chemotaxis, whereas cheA1 and cheY1 mutants retained chemotaxis ability almost equal to that of the wild-type (WT) strain. Although WT and cheY1 mutants of Pta6605 caused severe disease symptoms on host tobacco leaves, the cheA2 and cheY2 mutants did not, and symptom development with cheA1 depended on the inoculation method. These results indicate that chemotaxis genes located in cluster II are required for optimal chemotaxis and host plant infection by Pta6605 and that cluster I may partially contribute to these phenotypes. [ABSTRACT FROM AUTHOR]

Many pathogenic bacteria require flagella-mediated motility to colonise and persist in their hosts. Helicobacter pylori and Campylobacter jejuni are flagellated epsilonproteobacteria associated with several human pathologies, including gastritis, acute diarrhea, gastric carcinoma and neurological disorders. In both species, glycosylation of flagellin with an unusual sugar pseudaminic acid (Pse) plays a crucial role in the biosynthesis of functional flagella, and thereby in bacterial motility and pathogenesis. Pse is found only in pathogenic bacteria. Its biosynthesis via six consecutive enzymatic steps has been extensively studied in H. pylori and C. jejuni. This review highlights the importance of flagella glycosylation and details structural insights into the enzymes in the Pse pathway obtained via a combination of biochemical, crystallographic, and mutagenesis studies of the enzyme-substrate and -inhibitor complexes. It is anticipated that understanding the underlying structural and molecular basis of the catalytic mechanisms of the Pse-synthesising enzymes will pave the way for the development of novel antimicrobials. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the virulence of Staphylococcus aureus in a controlled animal study using the standard sterile gauze and negative pressure wound therapy (NPWT), including activation of agr, gene expression and production of virulence foctors and depth of bacterial invasion. The tissue specimens were harvested on days 0 (6 h after bacterial inoculation), 2, 4, 6, and 8 at the center of wound beds. Laser scanning confocal microscopy was performed to obtain bioluminescent images which were used to measure the depth of bacterial invasion. The agrA expression of S.aureus and the transcription and production of virulence factors including Eap, Spa and α-toxin were significantly different. The bacterial invasion depth was significantly less with effect of NPWT. The markedly different activation of quorum sensing systems that enable cell-to-cell communication and regulation of numerous colonization and virulence factors result in distinct gene expression and pathogenicity over time in different microenvironment. Thus, the agr system represents a fundamental regulatory paradigm that can encompass different adaptive strategies and accommodate horizontally acquired virulence determinants. [ABSTRACT FROM AUTHOR]

Bacteria have evolved a variety of different signal transduction mechanisms. However, the cognate signal molecule for the very large amount of corresponding sensor proteins is unknown and their functional annotation represents a major bottleneck in the field of signal transduction. The knowledge of the signal molecule is an essential prerequisite to understand the signalling mechanisms. Recently, the identification of signal molecules by the high-throughput protein screening of commercially available ligand collections using differential scanning fluorimetry has shown promise to resolve this bottleneck. Based on the analysis of a significant number of different ligand binding domains (LBDs) in our laboratory, we identified two issues that need to be taken into account in the experimental design. Since a number of LBDs require the dimeric state for ligand recognition, it has to be assured that the protein analysed is indeed in the dimeric form. A number of other examples demonstrate that purified LBDs can contain bound ligand which prevents further binding. In such cases, the apo-form can be generated by denaturation and subsequent refolding. We are convinced that this approach will accelerate the functional annotation of sensor proteins which will help to understand regulatory circuits in bacteria. [ABSTRACT FROM AUTHOR]

Pathogenic bacteria secrete pore-forming toxins (PFTs) to selectively defend against immune cells and to break through cellular barriers in the host. Understanding how PFTs attack cell membranes is not only essential for therapeutic intervention but for designing agents to deliver drugs to specific human cell subtypes, for example in anti-cancer or anti-viral therapies. Many toxins contain accessory domains that help recognize specific molecular epitopes on the membranes of target cells, including proteins, carbohydrates, and lipids. Here we report NMR assignments for the 94-residue 10 kDa C-terminal accessory domain of Bacillus cereus hemolysin II, HlyIIC, that has no known structural or functional homologues. The HlyIIC domain exists in a dynamic equilibrium due to cis/trans isomerization of its Gly86-Pro87 peptide bond. The cis and trans forms are about equally populated and are in slow exchange on the NMR timescale, giving rise to separate signals for approximately half of the residues in the domain. Assignments for the cis and trans forms were achieved with the aid of a P87M mutant that stabilizes the trans form, and separate sequential walks for the two forms in 3D NMR spectra of the wild-type HlyIIC. Based on backbone chemical shifts, the domain has a α1-α2-β1-β2-β3-β4-α3-β5 order of secondary structure elements. The last strand in the trans form and in the P87M mutant is shortened near Pro87 compared to the cis form. Both cis/trans isomerization and the P87M mutation cause large chemical shift changes throughout HlyIIC, suggesting that the proline is important in stabilizing the structure of the domain. The NMR assignments pave the way for solving the structures of the multiple conformational forms of HlyIIC and establishing their mechanism of interconversion. [ABSTRACT FROM AUTHOR]

Group A Streptococcus (GAS) is a human pathogen causing a wide range of mild to severe and life-threatening diseases. The GAS M1 protein is a major virulence factor promoting GAS invasiveness and resistance to host innate immune clearance. M1 displays an irregular coiled-coil structure, including the B-repeats that bind fibrinogen. Previously, we found that B-repeat stabilisation generates an idealised version of M1 (M1*) characterised by decreased fibrinogen binding in vitro. To extend these findings based on a soluble truncated version of M1, we now studied the importance of the B-repeat coiled-coil irregularities in full length M1 and M1* expressed in live GAS and tested whether the modulation of M1-fibrinogen interactions would open up novel therapeutic approaches. We found that altering either the M1 structure on the GAS cell surface or removing its target host protein fibrinogen blunted GAS virulence. GAS expressing M1* showed an impaired ability to adhere to and to invade human endothelial cells, was more readily killed by whole blood or neutrophils and most importantly was less virulent in a murine necrotising fasciitis model. M1-mediated virulence of wild-type GAS was strictly dependent on the presence and concentration of fibrinogen complementing our finding that M1-fibrinogen interactions are crucial for GAS virulence. Consistently blocking M1-fibrinogen interactions by fragment D reduced GAS virulence in vitro and in vivo. This supports our conclusion that M1-fibrinogen interactions are crucial for GAS virulence and that interference may open up novel complementary treatment options for GAS infections caused by the leading invasive GAS strain M1. [ABSTRACT FROM AUTHOR]

Our knowledge of the molecular mechanisms of urinary tract infection (UTI) pathogenesis has advanced greatly in recent years. In this review, we provide a general background of UTI pathogenesis, followed by an update on the mechanisms of UTI susceptibility, with a particular focus on genetic variation affecting innate immunity. The innate immune response of the host is critically important in the antibacterial defence mechanisms of the urinary tract, and bacterial clearance normally proceeds without sequelae. However, slight dysfunctions in these mechanisms may result in acute disease and tissue destruction. The symptoms of acute pyelonephritis are caused by the innate immune response, and inflammation in the urinary tract decreases renal tubular function and may give rise to renal scarring, especially in paediatric patients. In contrast, in children with asymptomatic bacteriuria (ABU), bacteria persist without causing symptoms or pathology. Pathogenic agents trigger a response determined by their virulence factors, mediating adherence to the urinary tract mucosa, signalling through Toll-like receptors (TLRs) and activating the defence mechanisms. In ABU strains, such virulence factors are mostly not expressed. However, the influence of the host on UTI severity cannot be overestimated, and rapid progress is being made in clarifying host susceptibility mechanisms. For example, genetic alterations that reduce TLR4 function are associated with ABU, while polymorphisms reducing IRF3 or CXCR1 expression are associated with acute pyelonephritis and an increased risk for renal scarring. It should be plausible to 'individualize' diagnosis and therapy by combining information on bacterial virulence and the host response. [ABSTRACT FROM AUTHOR]

Bordetella pertussis, the etiological agent of whooping cough, belongs to the bacterial pathogens first described in the so-called golden era of microbiology more than 100 years ago. In the course of the following decades, several other closely related pathogens were described which are nowadays classified in the genus Bordetella together with B. pertussis. These are the human and animal pathogens B. parapertussis, B. bronchiseptica and B. avium which are of high medical or veterinary interest, and which, together with B. pertussis, are referred to as the “classical” Bordetella species. Only in the past 15 years, several additional species were classified in the genus, frequently isolated from patients with underlying disease, animals or from the environment. Very little is known about most of these bacteria. In the present review, the current knowledge about these “new” Bordetella species is briefly summarized. [ABSTRACT FROM AUTHOR]

The contribution of iron transporter systems encoded by feo genes to the pathogenic traits of streptococci is largely unknown, despite the fact that those systems are required for the full virulence of several gram-negative bacterial species. In this work, we show that the swine pathogen and zoonotic agent Streptococcus suis has a feoAB operon similar to that encoding an iron transporter system in Escherichia coli. Electrophoretic mobility assays and transcriptional analyses confirmed that the expression of S. suis feo genes is under the negative control of the ferric uptake regulator (Fur) protein. In vivo trials in mice using a feoB defective mutant strain were carried out to investigate the contribution of this gene to the virulence of S. suis. The results showed that the median lethal dose (LD50) of the mutant was approximately 10-fold higher than that of the wild-type parent strain. These data suggest that the Feo metal transporter plays a significant role in streptococcal infectious disease. This is in contrast to previous results reported for this same gene in other gram-positive bacterial species. [ABSTRACT FROM AUTHOR]

There are few reports on urinary tract infections caused by Haemophilus influenzae or Haemophilus parainfluenzae in children. The true incidence is not known, since bacteria of Haemophilus species do not grow in standard urine culture media. With the objective of investigating the occurrence and character of urinary tract infections (UTIs) caused by Haemophilus bacteria in children, we searched the files of our UTI clinic. Over a 24-year period 36 children with Haemophilus spp. bacteriuria were identified out of a total of more than 5,000 UTI episodes. There was a significant gender difference in that Haemophilus influenzae dominated in girls and Haemophilus parainfluenzae in boys. With one exception, all children had important urinary tract abnormalities, such as malformation, gross reflux or bladder dysfunction. Permanent renal damage was seen in 25. We conclude that growth of Haemophilus bacteria in urine is associated with serious urinary tract abnormalities. The inability of bacteria of the Haemophilus species to grow in standard media commonly used for culture of uropathogens suggests that the true frequency of these strains as a cause of urinary tract infections is underestimated. [ABSTRACT FROM AUTHOR]

A previously optimized Escherichia coli two-plasmid system was used to identify Mycobacterium tuberculosis promoters recognized by RNA polymerase containing the M. tuberculosis stress response sigma factor σF. The method allowed the identification of five new σF-dependent promoters. Transcriptional start points of the promoters were determined by high-resolution S1-nuclease mapping using RNA prepared from E. coli containing the two-plasmid system. The promoters were confirmed by an in vitro transcription assay. The Mycobacterium smegmatis and Mycobacterium tuberculosis core RNA polymerases, after complementation with σF, were able to recognize all the five promoters. All the promoters contained sequences highly similar to the sequence of the previously identified M. tuberculosis σF-dependent promoter, usfXp1. Comparison of the promoters revealed a σF consensus sequence GtTtga-N14–18–GGGTAT. The σF-dependent promoters may govern expression of genes encoding a transcription regulator homologous to the response regulators of bacterial two-component signal transduction systems and proteins with unknown function. [ABSTRACT FROM AUTHOR]

A previously optimized Escherichia coli two-plasmid system was used to identify Mycobacterium tuberculosis promoters recognized by RNA polymerase containing the M. tuberculosis stress response sigma factor σF. The method allowed the identification of five new σF-dependent promoters. Transcriptional start points of the promoters were determined by high-resolution S1-nuclease mapping using RNA prepared from E. coli containing the two-plasmid system. The promoters were confirmed by an in vitro transcription assay. The Mycobacterium smegmatis and Mycobacterium tuberculosis core RNA polymerases, after complementation with σF, were able to recognize all the five promoters. All the promoters contained sequences highly similar to the sequence of the previously identified M. tuberculosis σF-dependent promoter, usfXp1. Comparison of the promoters revealed a σF consensus sequence GtTtga-N14–18–GGGTAT. The σF-dependent promoters may govern expression of genes encoding a transcription regulator homologous to the response regulators of bacterial two-component signal transduction systems and proteins with unknown function. [ABSTRACT FROM AUTHOR]

Many oral pathologies, such as dental caries, periodontal disease and peri-implantitis are plaque-related. Dental plaque is a microbial biofilm formed by organisms tightly bound to a solid substrate and each other by means of an exopolymer matrix. Bacteria exhibit different properties when contained within a biofilm. Knowing the mechanisms controlling the formation and development of biofilms can help to understand the emergence and progression of such pathologies and to plan effective treatment. Most periodontal pathogens are common saprophytes of the oral cavity, expressing their virulence only in a susceptible host or when some changes come about in the oral environment. Physical, metabolic and physiological interactions may cause positive or negative effects among the various microbiota present. Such mechanisms of antagonism/synergy select the bacterial population and alterations of its composition affect the balance with the host and may lead to pathology. The effectiveness of antimicrobial agents, as measured through in vitro tests, is dramatically reduced in vivo due to the properties of the microbial community: mature, intact biofilms are less sensitive to such agents, as the exopolymer matrix, bacterial enzymes and slow growth rate hinder the action of chemotherapeutic agents. The present literature review aims to examine the most representative studies, focusing on the characteristics of bacterial communities and the crucial shift from oral health to plaque-related diseases. [ABSTRACT FROM AUTHOR]

Comparison of the putative iteron-binding proteins of lambdoid phages allows us to propose that in the case of lambdoid replication modules, the units on which natural selection acts do not coincide with the open reading frames. Rather, the first replication gene is split into two segments, and its 3′ part (corresponding to the C-terminal domain of the iteron-binding protein) forms one unit with the second gene. We also propose from the phylogenetic analysis of phage-encoded homologs of E. coli DnaB and DnaC, that the recombination with the host sequences is not frequent. Accessory ATP-ases for helicase loading ( E. coli DnaC homologs) may not be universal replication proteins. Our analysis may suggest that the bacterial helicase loaders might be of phage origin. The comparison of DnaC homologs of enterobacteria and enterobacterial phages supports the experimental data on residues important in interaction with DnaB. We propose that construction of plasmids carrying the replication origins of lambdoid prophages could be useful not only in further research on DNA replication but also on the role of these prophages in shuttling genes for bacterial virulence. The phage replication sequences could be also useful for identification of clinical enterobacterial isolates. [ABSTRACT FROM AUTHOR]

Copyright of Langenbecks Archiv fuer Chirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The last decade has provided new insight into the mechanisms of host-parasite interactions in the urinary tract. Reduction of host resistance appears to reduce the requirement for bacterial virulence, whereas the resistant host becomes infected with bacteria of high virulence. In the resistant host, bacterial virulence can be defined as the sum of properties required to colonize the urinary tract and induce tissue reactions. The ability to attach to uroepithelial cells is the single property most frequently associated with pyelonephritogenic clones. Attachment to the Galα1-4Galβ-containing receptors promotes localization of bacteria to the kidney and the induction of lipopolysaccharide-mediated inflammation. Other virulence factors, defined by increased frequency in acute pyelonephritis compared with asymptomatic bacteriuria, include haemolysin and aerobactin production. Among the factors which influence the natural resistance to urinary tract infection are urinary flow and reactivity to endotoxin. The resistance induced by natural exposure to infection or immunization may be protective in experimental models, but the importance of this is not yet defined. The localization, severity and sequelae of urinary tract infection are determined by the balance between bacterial virulence and host resistance. Although disease is a result of the interaction between bacterial virulence and host resistance, these components are discussed separately for clarity. [ABSTRACT FROM AUTHOR]

Copyright of Langenbecks Archiv fuer Chirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)