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• W2116065003 abstract "ABSTRACT Bacteria have evolved strategies to resist killing by antimicrobial peptides (APs), important effectors of innate immunity. The sap (sensitivity to antimicrobial peptides) operon confers resistance to AP-mediated killing of Salmonella . We have recently shown that sapA gene expression is upregulated in the middle ear in a chinchilla model of nontypeable Haemophilus influenzae (NTHI)-induced otitis media. Based on these findings, we constructed an NTHI strain containing a Lux reporter plasmid driven by the sapA promoter and demonstrated early yet transient expression of the sap operon within sites of the chinchilla upper airway upon infection. We hypothesized that the sap operon products mediate NTHI resistance to APs. In order to test this hypothesis, we constructed a nonpolar mutation in the sapA gene of NTHI strain 86-028NP, a low-passage-number clinical isolate. The sapA mutant was approximately eightfold more sensitive than the parent strain to killing by recombinant chinchilla β-defensin 1. We then assessed the ability of this mutant to both colonize and cause otitis media in chinchillas. The sapA mutant was significantly attenuated compared to the parent strain in its ability to survive in both the nasopharynx and the middle ear of the chinchilla. In addition, the mutant was impaired in its ability to compete with the parent strain in a dual-strain challenge model of infection. Our results indicate that the products of the sap operon are important for resisting the activity of APs and may regulate, in part, the balance between normal carriage and disease caused by NTHI." @default.
• W2116065003 created "2016-06-24" @default.
• W2116065003 creator A5033040498 @default.
• W2116065003 creator A5050515581 @default.
• W2116065003 creator A5068983530 @default.
• W2116065003 date "2005-01-01" @default.
• W2116065003 modified "2023-10-16" @default.
• W2116065003 title "A Mutation in the <i>sap</i> Operon Attenuates Survival of Nontypeable <i>Haemophilus influenzae</i> in a Chinchilla Model of Otitis Media" @default.
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• W2116065003 doi "https://doi.org/10.1128/iai.73.1.599-608.2005" @default.
• W2116065003 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/538956" @default.
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