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Down-regulation of antioxidant enzymes in P. aeruginosa biofilms may enhance the rate of mutagenic events due to the accumulation of DNA damage. Since P. aeruginosa forms biofilms in the CF lung, this mode of growth may enhance the direct selection of antibiotic-resistant organisms in CF patients and also increase the opportunity to derive permanent hypermutators thereby providing a further source of antibiotic-resistant mutants in the CF lung.

The need for new antimicrobial agents is becoming one of the most urgent requirements in modern medicine. The venoms of many different species are rich sources of biologically active components and various therapeutic agents have been characterized including antimicrobial peptides (AMPs). Due to their potent activity, low resistance rates and unique mode of action, AMPs have recently received much attention. This review focuses on AMPs from the venoms of scorpions and examines all classes of AMPs found to date. It gives details of their biological activities with reference to peptide structure. The review examines the mechanism of action of AMPs and with this information, suggests possible mechanisms of action of less well characterised peptides. Finally, the review examines current and future trends of scorpion AMP research, by discussing recent successes obtained through proteomic and transcriptomic approaches.

These data show that daptomycin-induced loss of Mg(2+) and ATP occurs in conjunction with the previously reported leakage of K(+) and membrane depolarization. We propose that the lethal activity of daptomycin is not simply due to loss of K(+) and probably involves more general damage to the membrane.

Oxazolidinone and pleuromutilin antibiotics are currently used in the treatment of staphylococcal infections. Although both antibiotics inhibit protein synthesis and have overlapping binding regions on 23S rRNA, the potential for cross-resistance between the two classes through target site mutations has not been thoroughly examined. Mutants of Staphylococcus aureus resistant to linezolid were selected and found to exhibit crossresistance to tiamulin, a member of the pleuromutilin class of antibiotics. However, resistance was unidirectional because mutants of S. aureus selected for resistance to tiamulin did not exhibit cross-resistance to linezolid. This contrasts with the recently described PhLOPS A phenotype, which confers resistance to both oxazolidinones and pleuromutilins. The genotypes responsible for the phenotypes we observed were examined. Selection with tiamulin resulted in recovery of mutants with changes in the single-copy rplC gene (Gly155Arg, Ser158Leu, or Arg149Ser), whereas selection with linezolid led to recovery of mutants with changes (G2576U in 23S rRNA) in all five copies of the multicopy operon rrn. In contrast, cross-resistance to linezolid was exhibited by tiamulin-resistant mutants generated in a single-copy rrn knockout strains of Escherichia coli, illustrating that the copy number of 23S rRNA is the limiting factor in the selection of 23S rRNA tiamulinresistant mutants. The interactions of linezolid and tiamulin with the ribosome were modeled to seek explanations for resistance to both classes in the 23S rRNA mutants and the lack of cross-resistance between tiamulin and linezolid following mutation in rplC.Linezolid (LZD) is a synthetic antimicrobial agent belonging to the oxazolidinone class. It inhibits bacterial protein synthesis and has recently been introduced for the treatment of infections caused by gram-positive pathogens, including Staphylococcus aureus. Despite early predictions that LZD would display a low potential for the development of resistance, resistant clinical isolates of S. aureus with a G2576U mutation in all copies of the 23S rRNA gene have, unfortunately, emerged following prolonged therapy with the agent (13,23,24).Pleuromutilins, such as tiamulin (TML) and valnemulin (VML), are used in veterinary medicine to treat infections caused by gram-positive pathogens. TML, the most widely used pleuromutilin, is a semisynthetic inhibitor of bacterial protein synthesis, most commonly used in the treatment of Brachyspira hyodysenteria infections in swine. Another pleuromutilin derivative, retapamulin, has recently been approved for the treatment of impetigo caused by methicillin-susceptible S. aureus and Streptococcus pyogenes (6,19), and further members of the pleuromutilin class are in development as potential oral agents for systemic application (Nabriva, Vienna, Austria).Pleuromutilin resistance has been identified in clinical isolates of Brachyspira spp. and in Escherichia coli, Streptococcus pyogenes, and S. aureus isolates selected in vitro (1,2,5,8,9,18). Furtherm...

XF-70 and XF-73 remained highly active against various forms of slow-growing or non-dividing S. aureus. The results support the hypothesis that membrane-active agents may be particularly effective in eradicating slow- or non-growing bacteria and suggest that XF-70 and XF-73 could be utilized to treat staphylococcal infections where the organisms are only dividing slowly, such as biofilm-associated infections of prosthetic devices.

The PL assay is unsuitable for detection of membrane-damaging agents in S. aureus. The other assays, including the BG assay, detect membrane damage. The OD assay should be sufficient for most purposes since it is effective, rapid and cheap to perform. Studies requiring maximum sensitivity and discrimination should employ the ATP assay.