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Many strains of community-acquired meticillin-resistant Staphylococcus aureus (MRSA) have a pore-forming leukotoxin, known as Panton-Valentine leukocidin (PVL), which can cause severe necrotising pneumonia. Linezolid (LZD) is a new antibacterial agent with potent antibacterial activity against MRSA. In this study, a mouse model of haematogenous pulmonary infection was used to compare the efficacies of LZD and vancomycin (VAN) against pulmonary infection caused by PVL-positive S. aureus. Following antibiotic administration for 3 days, the number of viable bacteria (mean+/-standard error of the mean) in the control, VAN and LZD groups was 6.77+/-0.14, 5.29+/-0.27 and 4.25+/-0.33 log colony-forming units/lung, respectively. LZD significantly decreased the number of viable bacteria in the lungs compared with the control and VAN groups (P<0.05). The survival rate at Day 7 post-inoculation was higher in the LZD group (100%) than in the VAN group (50%) or the control group (0%). Histopathological examination and cytokine analysis also showed the beneficial efficacy of LZD compared with VAN. In conclusion, LZD significantly reduced bacterial numbers and inflammation in a mouse model of PVL-positive S. aureus haematogenous infection and improved the survival rate of infected mice compared with VAN. LZD is clinically effective against PVL-positive S. aureus.

A series of epidemics of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) have occurred in Australia, starting in Western Australia in the early 1990s, in the Northern Territory soon thereafter and in eastern states in the mid 1990s. The Western Australian epidemic has been due mainly to Panton-Valentine leukocidin (PVL)-negative clones, whilst PVL-positive clones have predominated in the east. More recently, the major epidemic clones have spread throughout the country, whilst multiple new minor clones have emerged, mainly in Western Australia. A total of 45 clones of CA-MRSA have been detected in Australia to date: 30 of these carry SCCmec IV, 6 carry SCCmec V and 9 carry novel SCCmec types. Overall, CA-MRSA clones have been associated predominantly with skin and soft-tissue infections. PVL-positive clones have been associated with furunculosis, necrotising pneumonia and osteomyelitis and have caused fatalities in otherwise healthy children and young adults. Initial treatment of these infections remains problematic, as it is frequently inappropriate. Of particular concern, healthcare-associated acquisition of CA-MRSA clones is now increasing, although major hospital outbreaks have not occurred yet.

Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus is emerging as a serious problem worldwide. Whilst usually causing skin and soft-tissue infections, particularly recurrent abscesses, there has in the last 10 years been an increase in the incidence of an associated devastating pneumonia affecting previously healthy young people and associated with a very high mortality. There are no evidence-based guidelines to consult for the management of PVL-associated staphylococcal pneumonia. The literature contains less than 100 cases, with widely differing antimicrobial therapies and the occasional use of other adjunctive therapies such as intravenous immunoglobulin, activated protein C and extracorporeal membrane oxygenation. This literature review focuses on the salient features of diagnosis and management, with particular attention to the choice of antimicrobials.

Streptococcal pyrogenic exotoxins A (SPE-A) and B (SPE-B) have been implicated in the pathogenesis of serious group A streptococcal infections including streptococcal toxic shock-syndrome. Current antibiotics used for the treatment of these infections are penicillin and clindamycin. The effects of sub- and suprainhibitory concentrations of penicillin and clindamycin were evaluated in 14 isolates of Streptococcus pyogenes that were fully susceptible to both antibiotics. Clindamycin was superior to penicillin in reducing the production of SPE-A and SPE-B by invasive and non-invasive Dutch group A streptococcal isolates in vitro.

Expanded bed chromatography was used for the recovery and purification of modified Pseudomonas aeruginosa exotoxin A. The exotoxin accumulates in the periplasmic space of E. coli BL21 (lambda DE3), was released from the cells by osmotic shock and captured by applying the open cell suspension directly to an anion exchanger (STREAMLINE DEAE) using an expanded bed (STREAMLINE) column. Processing of 4.5 kg of E. coli using the expanded bed process was 3 times faster and did not require clarification of the bacterial extract, in comparison with the conventional purification method. Also, the recovered protein solution was 3 times more concentrated and the yield slightly higher.

Procedures have been devised for producing high yields of purified recombinant PE40, a protein important for the development of the anti-AIDS therapeutic, sCD4-PE40. PE40 is a truncated form of the bacterial toxin, Pseudomonas exotoxin A; it lacks the cell-binding domain, but retains domains II and III that are involved in membrane translocation and inhibition of protein synthesis in eukaryotic cells. Expression vectors in Escherichia coli encoding PE40 synthesized the product as a soluble protein under control of the T7 promoter. The expression capabilities of transformants of E. coli BL21(DE3) were highly unstable. Expression levels (secreted and total) were evaluated in shake flasks and at the 10-1 scale at 27 degrees C and 37 degrees C, and following induction by IPTG or lactose. The cell-free media from the batch process was applied directly to a Cibacron blue F3GA-chromatographic medium and PE40 was eluted by nicotinamide in high yield and purity. This purification strategy was based on the structural similarity of the blue dye to NAD, a natural substrate for domain III of PE40. Green and red dye-ligand chromatography steps removed nicotinamide as well as minor residual E. coli proteins from PE40. Reversed-phase liquid chromatography peptide maps of purified PE40 were characterized by electrospray ionization mass spectrometry to determine the sequence and verify disulfide bonding.

The ability of enterotoxigenic strains of Aeromonas hydrophila and Aeromonas sobria to produce exotoxins (enterotoxin and haemolysin) in a meat extract at low temperatures (5 and 12 degrees C) was investigated. All three strains incubated at 12 degrees C were enterotoxigenic and haemolytic in the meat extract after 5 days. At 5 degrees C, five of the six strains tested were able to produce these exotoxins after 8 days incubation while one strain was neither enterotoxigenic nor haemolytic after 5, 8 and 11 days. The possible involvement of performed toxin(s) in Aeromonas gastroenteritis is also discussed.