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Previously it has been demonstrated that Staphylococcus aureus is sensitive toward Pseudomonas-secreted exotoxins, which preferentially target the electron transport chain in staphylococci. Here it is shown that a subpopulation of S. aureus survives these respiratory toxins of Pseudomonas aeruginosa by selection of the small-colony variant (SCV) phenotype. Purified pyocyanin alone causes the same effect. A hemB mutant of S. aureus survives cocultivation with P. aeruginosa without a decrease in CFU.Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic pathogens and frequently coinfect the lungs of patients with cystic fibrosis (CF). P. aeruginosa excretes an arsenal of small respiratory inhibitors, like pyocyanin (5), hydrogen cyanide (2), or quinoline N-oxides (9), that may act against the commensal microbiota as well as host cells. Previously it has been demonstrated that S. aureus is sensitive toward the toxic products generated by P. aeruginosa and that these exotoxins preferentially target the electron transport chain (17).Staphylococcal species can be divided into two groups: the sensitive group, comprising pathogenic species such as S. aureus and S. epidermidis, and the resistant group, represented by nonpathogenic species such as S. carnosus, S. piscifermentans, and S. gallinarum. The resistance in the latter group was due to cydAB genes, which encode a pyocyanin-and cyanide-resistant cytochrome bd quinol oxidase (17). It has also been shown that the resistant or sensitive phenotype is determined by the CydB subunit, which is part of the cytochrome bd quinol oxidase of S. aureus. Despite its sensitivity to these exotoxins, S. aureus has frequently been coisolated with P. aeruginosa from the skin, eyes, and catheter infections and from the lungs of patients with CF. The aim of this study is to elucidate the escape mechanism of S. aureus by cocultivating S. aureus and P. aeruginosa. The findings indicate that a subpopulation of the staphylococcal community can survive in the presence of P. aeruginosa by the selection of small-colony variants (SCVs), which usually are defective in the electron transport chain. SCVs grow as tiny, nonpigmented colonies and are auxotrophic to hemin, menadione, or thymidine (14). Here we show that both a culture supernatant of P. aeruginosa and purified pyocyanin select for the SCV phenotype in S. aureus.Cocultivation of S. aureus and P. aeruginosa can select for S. aureus SCVs. S. aureus was grown in monoculture or in coculture with P. aeruginosa (1:1, optical density at 578 nm) in tryptic soy broth (TSB) medium under biofilm or planktonic conditions. Biofilm studies using S. aureus(pCtuf-gfp) and P. aeruginosa::pUT-tell-rfp grown in TSB medium supplemented with 0.5% glucose under static conditions for 36 h showed that both S. aureus and P. aeruginosa form thicker biofilm in monocultures, while in a mixed biofilm with P. aeruginosa only few S. aureus cells were visible (Fig. 1A).Titers of S. aureus grown under planktonic conditions in monoculture and in coculture w...

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The Staphylococcus carnosus genome has the highest GC content of all sequenced staphylococcal genomes, with 34.6%, and therefore represents a species that is set apart from S. aureus, S. epidermidis, S. saprophyticus, and S. haemolyticus. With only 2.56 Mbp, the genome belongs to a family of smaller staphylococcal genomes, and the ori and ter regions are asymmetrically arranged with the replichores I (1.05 Mbp) and II (1.5 Mbp). The events leading up to this asymmetry probably occurred not that long ago in evolution, as there was not enough time to approach the natural tendency of a physical balance. Unlike the genomes of pathogenic species, the TM300 genome does not contain mobile elements such as plasmids, insertion sequences, transposons, or STAR elements; also, the number of repeat sequences is markedly decreased, suggesting a comparatively high stability of the genome. While most S. aureus genomes contain several prophages and genomic islands, the TM300 genome contains only one prophage, ⌽TM300, and one genomic island, SCA1, which is characterized by a mosaic structure mainly composed of species-specific genes. Most of the metabolic core pathways are present in the genome. Some open reading frames are truncated, which reflects the nutrient-rich environment of the meat starter culture, making some functions dispensable. The genome is well equipped with all functions necessary for the starter culture, such as nitrate/nitrite reduction, various sugar degradation pathways, two catalases, and nine osmoprotection systems. The genome lacks most of the toxins typical of S. aureus as well as genes involved in biofilm formation, underscoring the nonpathogenic status.It has been known for a long time that staphylococci play a role in the fermentation of dry sausage (52). At first, they were regarded as micrococci, but it turned out that these micrococci were wrongly classified and were in fact staphylococci. Based on DNA/DNA hybridization, biochemical properties, and cell wall composition, these staphylococci formed a new species, which was named Staphylococcus carnosus because the bacteria can be isolated from meat fermentation products and have been used since the 1950s as a starter culture (64).One of the main advantages of starter cultures in fermentedfood processing is that the fermentation and ripening process can be carried out under controlled conditions. In this way, food poisoning and food spoilage microorganisms can be suppressed, and the course of the fermentation process and its termination can be more reliably monitored. During the ripening process of dry sausage, S. carnosus exerts several desired functions (5, 14, 40). First, S. carnosus gradually reduces nitrate to nitrite (50). The advantages of this reaction are that the nitrate concentration is lowered and that nitrite can combine with myoglobin to form nitrosomyoglobin, which results in the typical red color. In the second step, nitrite is then further reduced to ammonia, thus lowering the unbound nitrite concentration (51). Other advantages are d...

bPolymicrobial infections involving Staphylococcus aureus exhibit enhanced disease severity and morbidity. We reviewed the nature of polymicrobial interactions between S. aureus and other bacterial, fungal, and viral cocolonizers. Microbes that were frequently recovered from the infection site with S. aureus are Haemophilus influenzae, Enterococcus faecalis, Pseudomonas aeruginosa, Streptococcus pneumoniae, Corynebacterium sp., Lactobacillus sp., Candida albicans, and influenza virus. Detailed analyses of several in vitro and in vivo observations demonstrate that S. aureus exhibits cooperative relations with C. albicans, E. faecalis, H. influenzae, and influenza virus and competitive relations with P. aeruginosa, Streptococcus pneumoniae, Lactobacillus sp., and Corynebacterium sp. Interactions of both types influence changes in S. aureus that alter its characteristics in terms of colony formation, protein expression, pathogenicity, and antibiotic susceptibility.