Bacteria of the genus Staphylococcus are common pathogens responsible for a broad spectrum of human and animal infections and belong to the most important etiological factors causing food poisoning. Because of rapid increase in the prevalence of isolation of staphylococci resistant to many antibiotics, there is an urgent need for the development of new alternative chemotherapeutics. A number of studies have recently demonstrated the strong potential of peptidoglycan hydrolases (PHs) to control and treat infections caused by this group of bacteria. PHs cause rapid lysis and death of bacterial cells. The review concentrates on enzymes hydrolyzing peptidoglycan of staphylococci. Usually, they are characterized by high specificity to only Staphylococcus aureus cell wall components; however, some of them are also able to lyse cells of other staphylococci, e.g., Staphylococcus epidermidis-human pathogen of growing importance and also other groups of bacteria. Some PHs strengthen the bactericidal or bacteriostatic activity of common antibiotics, and as a result, they should be considered as component of combined therapy which could definitely reduced the development of bacterial resistance to both enzymes and antibiotics. The preliminary research revealed that most of these enzymes can be produced using heterologous, especially Escherichia coli expression systems; however, still much effort is required to develop more efficient and large-scale production technologies. This review discusses current state on knowledge with emphasis on the possibilities of application of PHs in the context of therapeutics for infections caused by staphylococci.

The aim of the study was phenotypic and genotypic analysis of 132 S. aureus strains isolated from mastitis in eastern Poland in respect to their biofilm formation ability. The analysis of the size polymorphism of fragment X in the gene encoding protein A (spa) revealed high genetic differentiation of the analyzed group of isolates. The ability of biofilm formation by the isolates was tested using two phenotypic methods. The Congo Red plate assay was found to be irreproducible and very subjective. More objective results were obtained using the spectrophotometric, microtiter plate assay. Most of the isolates, namely 76/132 (57.6 %) were classified as biofilm producers depending on the value of absorbance in the microtiter plate test. All of the isolates tested were found to possess both icaA and icaD genes, while the bap gene was absent in all strains.

The aim of this study was to analyze the resistance of Staphylococcus aureus isolates from bovine mastitis in the eastern part of Poland to a set of 20 antibiotics and three alternative agents: lysostaphin, nisin and polymyxin B. Eighty-six out of 123 examined isolates were susceptible to all 20 tested antibiotics (70%). The highest percentage of resistance was observed in the case of β-lactam antibiotics: amoxicillin (n=22, 17.9%), ampicillin (n=28, 22.8%), penicillin (n=29, 23.6%) and streptomycin (n=13; 10.6%). Twenty-five of the penicillin-resistant strains were found to carry the blaZ gene coding for β-lactamases. Two strains were found to be mecA positive and a few strains were classified as multidrug resistant (MDR), one of them was simultaneously resistant to six antibiotics. All strains, resistant to at least one antibiotic (n=37) and two control strains, were susceptible to lysostaphin with MIC values of 0.008–0.5 µg/ml (susceptibility breakpoint 32 µg/ml). Twenty-one (54%) isolates were susceptible to nisin. The MIC value of this agent for 17 (44%) strains was 51.2 µg/ml and was not much higher than the susceptibility breakpoint value (32 µg/ml). Polymyxin B was able to inhibit the growth of the strains only at a high concentration (32–128 µg/ml). The presented results confirmed the observed worldwide problem of spreading antibiotic resistance among staphylococci isolated from bovine mastitis; on the other hand, we have indicated a high level of bactericidal activity of nisin and especially lysostaphin.

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Oligopeptides incorporating N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP), an inhibitor of glucosamine-6-phosphate synthase, exhibited growth inhibitory activity against Candida albicans, with minimal inhibitory concentration values in the 0.05–50 μg mL-1 range. Uptake by the peptide permeases was found to be the main factor limiting an anticandidal activity of these compounds. Di- and tripeptide containing FMDP (F2 and F3) were transported by Ptr2p/Ptr22p peptide transporters (PTR) and FMDP-containing hexa-, hepta-, and undecapeptide (F6, F7, and F11) were taken up by the oligopeptide transporters (OPT) oligopeptide permeases, preferably by Opt2p/Opt3p. A phenotypic, apparent resistance of C. albicans to FMDP-oligopeptides transported by OPT permeases was triggered by the environmental factors, whereas resistance to those taken up by the PTR system had a genetic basis. Anticandidal activity of longer FMDP-oligopeptides was strongly diminished in minimal media containing easily assimilated ammonium sulfate or L-glutamine as the nitrogen source, both known to downregulate expression of the OPT genes. All FMDP-oligopeptides tested were more active at lower pH and this effect was slightly more remarkable for peptides F6, F7, and F11, compared to F2 and F3. Formation of isolated colonies was observed inside the growth inhibitory zones induced by F2 and F3 but not inside those induced by F6, F7, and F11. The vast majority (98%) of those colonies did not originate from truly resistant cells. The true resistance of 2% of isolates was due to the impaired transport of di- and to a lower extent, tripeptides. The resistant cells did not exhibit a lower expression of PTR2, PTR22, or OPT1–3 genes, but mutations in the PTR2 gene resulting in T422H, A320S, D119V, and A320S substitutions in the amino acid sequence of Ptr2p were found.

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The antifungal activity of 5-hydroxy-4-oxo-L-norvaline (HONV), exhibited under conditions mimicking human serum, may be improved upon incorporation of this amino acid into a dipeptide structure. Several HONV-containing dipeptides inhibited growth of human pathogenic yeasts of the Candida genus in the RPMI-1640 medium, with minimal inhibitory concentration values in the 32 to 64 μg mL −1 range. This activity was not affected by multidrug resistance that is caused by overexpression of genes encoding drug efflux proteins. The mechanism of antifungal action of HONV dipeptides involved uptake by the oligopeptide transport system, subsequent intracellular cleavage by cytosolic peptidases, and inhibition of homoserine dehydrogenase by the released HONV. The relative transport rates determined the anticandidal activity of HONV dipeptides.

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