TL;DR: Reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S. aureus, showing how commensal skin bacteria protect against pathogens and how dysbiosis of the skin microbiome can lead to disease.
Abstract: The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S. aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S. aureus The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis These AMPs were strain-specific, highly potent, selectively killed S. aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S. aureus These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.
TL;DR: The skin is a milieu for controlled bacterial growth, which supports the growth of commensal bacteria, which protect the host from pathogenic bacteria, and environmental and local factors, host immunity, and organism adherence and virulence are intricately related to cutaneous infection.
Abstract: The skin is a milieu for controlled bacterial growth. Skin supports the growth of commensal bacteria, which protect the host from pathogenic bacteria. Environmental and local factors, host immunity, and organism adherence and virulence are intricately related to cutaneous infection. Resident gram- positive bacteria include Staphylococcus , Micrococcus , and Corynebacterium sp . Staphylococcus aureus and Strepto coccus pyogenes are notoriously pathogenic in the skin. In order for bacteria to be pathogenic, they must be able to adhere to, grow on, and invade the host. Bacteria possess numerous virulence genes that allow for growth in these privileged niches. Epidermal infections caused by S. aureus and S. pyogenes include impetigo and ecthyma. Dermal infections consist of erysipelas, cellulitis, and necrotizing fasciitis. The pilosebaceous unit is involved in folliculitis, furunculosis, and carbunculosis. Moreover, S. aureus and S. pyogenes produce toxins that may elicit a superantigen response, causing massive release of cytokines. Staphylococcal scalded skin syndrome, toxic shock syndrome, and scarlet fever are all superantigen-mediated. Gram-negative organisms such as Pseudo monas aeruginosa , Pasteurella multocida , Capnocytophaga canimorsus , Bartonella sp ., Klebsiella rhinoscleromatis , and Vibrio vulnificus are not typical resident skin microflora but may cause cutaneous infection.
TL;DR: Ertapenem and piperacillin-tazobactam were each active against >98% of the enteric gram-negative rods, methicillin-sensitive S. aureus, and anaerobes, and antibiotic susceptibility results can help to inform therapeutic choices.
Abstract: As part of a United States-based multicenter clinical trial, conducted from 2001 to 2004, that compared ertapenem to piperacillin-tazobactam for the treatment of moderate-to-severe diabetic foot infections (DFIs), we obtained 454 pretreatment specimens from 433 patients. After debridement, the investigators collected wound specimens, mostly by curettage or biopsy, and sent them to the R. M. Alden Research Laboratory for aerobic and anaerobic culture. Among the 427 positive cultures, 83.8% were polymicrobial, 48% grew only aerobes, 43.7% had both aerobes and anaerobes, and 1.3% had only anaerobes. Cultures yielded a total of 1,145 aerobic strains and 462 anaerobic strains, with an average of 2.7 organisms per culture (range, 1 to 8) for aerobes and 2.3 organisms per culture (range, 1 to 9) for anaerobes. The predominant aerobic organisms were oxacillin-susceptible Staphylococcus aureus (14.3%), oxacillin-resistant Staphylococcus aureus (4.4%), coagulase-negative Staphylococcus species (15.3%), Streptococcus species (15.5%), Enterococcus species (13.5%), Corynebacterium species (10.1%), members of the family Enterobacteriaceae (12.8%), and Pseudomonas aeruginosa (3.5%). The predominant anaerobes were gram-positive cocci (45.2%), Prevotella species (13.6%), Porphyromonas species (11.3%), and the Bacteroides fragilis group (10.2%). Pure cultures were noted for 20% of oxacillin-resistant Staphylococcus aureus cultures, 9.2% of Staphylococcus epidermidis cultures, and 2.5% of P. aeruginosa cultures. Two or more species of Staphylococcus were present in 13.1% of the patients. Ertapenem and piperacillin-tazobactam were each active against >98% of the enteric gram-negative rods, methicillin-sensitive S. aureus, and anaerobes. Among the fluoroquinolones, 24% of anaerobes, especially the gram-positive cocci, were resistant to moxifloxacin; 27% of the gram-positive aerobes but only 6% of the members of the family Enterobacteriaceae were resistant to levofloxacin. Moderate-to-severe DFIs are typically polymicrobial, and almost half include anaerobes. Our antibiotic susceptibility results can help to inform therapeutic choices.
TL;DR: A chronology of key events and publications: 1.
Abstract: 3Wilt, F. H., Biochem. Biophys. Res. Commun., 11, 447 (1963). 7Brachet, J., et al., Biochim. Biophys. Acta, 72, 662 (1963). 8 Gross, P. R., and G. H. Cousineau, Exptl. Cell Res., in press. I Hultin, T., Exptl. Cell Res., 25, 405 (1961). 10 Wilt, F. H., and T. Hultin, Biochem. Biophys. Res. Commun., 9, 313 (1962). 11 Melton, C. R., Genetics, 48, 901 (1963). 12Tyler, A., Am. Zoologist, 3, 109 (1963). 13 Gross, P. R., W. Spindel, and G. H. Cousineau, Biocheem. Biophys. Res. Commun., 13, 405 (1963). 14 Cavanaugh, G., ed., Formulae and Methods of the Marine Biological Laboratory, IV (Woods Hole, 1956). 15 Herberg, R., Science, 128, 199 (1958). 16Bray, G., Anal. Biochem., 1, 279 (1960). 17 Lowry, O., et al., J. Biol. Chem., 193, 265 (1951). 18 Scherrer, K., and J. Darnell, Biochem. Biophys. Res. Commun., 7, 486 (1962). 19 Fraenkel-Conrat, H., B. Singer, and A. Tsugita, Virology, 14, 54 (1961). 20 Hurwitz, J., et al., these PROCEEDINGS, 48, 1222 (1962). 21 Reich, E., I. H. Goldberg, and M. Rabinowitz, Nature, 196, 743 (1962). 22 Levinthal, C., A. Keynan, and A. Higa, these PROCEEDINGS, 48, 1631 (1962). 23 Monier, R., et al., J. Mol. Biol., 5, 311 (1962). 24 Nemer, M., and S. G. Bard, Science, 140, 664 (1963). 25 Maggio, R., and C. Catalano, in preparation. 26 Hultin, T., Experientia, 7, 410 (1961). 27 Gross, P. R., and G. H. Cousineau, J. Cell Biol., 19, 260 (1963).
TL;DR: The hypothesis that the mechanism of action of penicillin is related to inhibition of a step in biosynthesis of the bacterial cell wall is led by the findings of a careful study of the composition of the cell walls of two strains of S. aureus.