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1.
Microb Genom ; 9(10)2023 10.
Article in English | MEDLINE | ID: mdl-37850987

ABSTRACT

Neisseria meningitidis (Nm) is a bacterial pathogen responsible for invasive meningococcal disease. Though typically colonizing the nasopharynx, multiple outbreaks of meningococcal urethritis were first reported in 2015-2016; outbreaks originally presumed to be caused by Neisseria gonorrhoeae (Ng). Genomic analysis revealed that the Nm isolates causing these outbreaks were a distinct clade, and had integrated gonococcal DNA at multiple genomic sites, including the gonococcal denitrification apparatus aniA-norB, a partial gonococcal operon of five genes containing ispD, and the acetylglutamate kinase gene argB with the adjacent gonococcal locus NGO0843. The urethritis isolates had also deleted the group C capsule biosynthesis genes cssA/B/C and csc, resulting in loss of capsule. Collectively, these isolates form the N. meningitidis urethritis clade (NmUC). Genomic analysis of recent (2016-2022) NmUC isolates revealed that the genomic features have been maintained in the clade, implying that they are important for NmUC's status as a urogenital pathogen. Furthermore, the analysis revealed the emergence of a sub-clade, designated NmUC-B, phylogenetically separated from the earlier NmUC-A. This sub-clade has integrated additional gonococcal alleles into the genome, including alleles associated with antimicrobial resistance. NmUC continues to adapt to a urethral niche and evolve as a urogenital pathogen.


Subject(s)
Gonorrhea , Meningococcal Infections , Neisseria meningitidis , Urethritis , Humans , Urethritis/epidemiology , Urethritis/microbiology , Meningococcal Infections/microbiology , Gonorrhea/microbiology , Genomics , Evolution, Molecular
2.
Cell Host Microbe ; 22(6): 746-756.e5, 2017 Dec 13.
Article in English | MEDLINE | ID: mdl-29199097

ABSTRACT

Coagulase-negative staphylococci (CoNS) and Staphylococcus aureus are part of the natural flora of humans and other mammals. We found that spent media from the CoNS species Staphylococcus caprae can inhibit agr-mediated quorum sensing by all classes of S. aureus. A biochemical assessment of the inhibitory activity suggested that the S. caprae autoinducing peptide (AIP) was responsible, and mass spectrometric analysis identified the S. caprae AIP as an eight-residue peptide (YSTCSYYF). Using a murine model of intradermal MRSA infection, the therapeutic efficacy of synthetic S. caprae AIP was evident by a dramatic reduction in both dermonecrotic injury and cutaneous bacterial burden relative to controls. Competition experiments between S. caprae and MRSA demonstrated a significant reduction in MRSA burden using murine models of both skin colonization and intradermal infection. Our findings indicate that important interactions occur between commensals that can impact disease outcomes and potentially shape the composition of the natural flora.


Subject(s)
Antibiosis , Quorum Sensing , Staphylococcal Infections/microbiology , Staphylococcal Skin Infections/microbiology , Staphylococcal Skin Infections/prevention & control , Staphylococcus/growth & development , Animals , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Disease Models, Animal , Mass Spectrometry , Mice , Peptides, Cyclic/chemistry , Peptides, Cyclic/metabolism
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