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Coagulase-negative staphylococci are dominant human skin colonizers, producing natural products that shape the community and prevent pathogen colonization. The molecular mechanisms by which these natural products mediate interbacterial competition are not fully understood. Here, we identify a plasmid-borne daptide bacteriocin (hominicin) from a human skin isolate of Staphylococcus hominis , which features an unusual N 2 - N 2 -dimethyl-1,2-propanediamine C-terminus. Heterologous expression of the reconstituted biosynthetic loci yields a daptide product of the same molecular mass that exhibits antimicrobial activity against the skin pathogen Staphylococcus aureus , with amino-modified termini being essential for activity. Membrane permeability and voltage-clamp lipid bilayer experiments support a mechanism by which the daptide rapidly dissipates the transmembrane potential by forming peptidic channels. Additionally, we identify a cognate homI gene that confers resistance against membrane damage. Finally, the purified daptide effectively protects mouse skin from S. aureus- induced epicutaneous injury, as evidenced by reduced bacterial burden, inflammation, and transepithelial water loss, highlighting its therapeutic potential for treating bacterial skin infections. Our findings elucidate a mechanism of action, biosynthesis, and resistance for a staphylococcal bacteriocin belonging to a class of natural products called daptides. Coagulase-negative staphylococci secrete natural products that prevent pathogen colonization. Here, the authors identify hominicin, a daptide bacteriocin produced by Staphylococcus hominis that has antimicrobial activity against a skin pathogen.

The ATM gene is mutated in ataxia‐telangiectasia (AT). Heterozygote female relatives of AT cases have a 2‐7fold increased risk of breast cancer. We previously reported high risks of breast cancer associated with certain ATM variants. To estimate the risks more precisely, we have examined two ATM variants, c.1066‐6T>G (IVS10‐6T>G) and c.4258C>T (p.Leu1420Phe), in additional cases and controls from the same Australian cohorts previously used to estimate the risk of breast cancer associated with c.1066‐6T>G. A total of 775 and 84 population‐based controls were genotyped for the c.1066‐6T>G and c.4258C>T ATM variants respectively, as were index cases from 378 and 373 non‐BRCA1/2 breast cancer families. Penetrance was estimated by Bayes factor analysis. The allele frequencies of ATM c.1066‐6T>G and c.4258C>T estimated from controls were 0.005 (95% CI=0.002 to 0.009) and 0.012 (95% CI=0.001 to 0.042), respectively. We identified three new breast cancer families with c.1066‐6T>G, and seven families with c.4258C>T. Combining with the two c.1066‐6T>G families previously reported, the estimated penetrance to age 70 of c.1066‐6T>G was 17.2% (95% CI=4.7% to 37.5%). For c.4258C>T, the estimated average penetrance was 4.8% (95% CI 1.7% to 10.1%). In conclusion, we found no evidence that the ATM c.4258C>T variant increases breast cancer risk, and little evidence that c.1066‐6T>G confers an elevated risk. Analysis of additional families will be necessary to define more precisely the risk, if any, associated with c.1066‐6T>G. © 2005 Wiley‐Liss, Inc.