ArticleMolecular microbiology2005
The penC mutation conferring antibiotic resistance in Neisseria gonorrhoeae arises from a mutation in the PilQ secretin that interferes with multimer stability.
Article in Molecular microbiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 96 citations in OpenAlex.
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- Current Susceptibility Surveillance and Distribution of Antimicrobial Resistance inPathogens (Basel, Switzerland) · 2022Review
- Novel small molecules that increase the susceptibility of Neisseria gonorrhoeae to cationic antimicrobial peptides by inhibiting lipid A phosphoethanolamine transferase.The Journal of antimicrobial chemotherapy · 2022Article
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- The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae.PLoS pathogens · 2020Article
- Exploration of theAntibiotics (Basel, Switzerland) · 2020Article
- Multiresistant Neisseria gonorrhoeae: a new threat in second decade of the XXI century.Medical microbiology and immunology · 2020Review
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- Using the genetic characteristics of Neisseria gonorrhoeae strains with decreased susceptibility to cefixime to develop a molecular assay to predict cefixime susceptibility.Sexual health · 2019Article
- Applications of genomics to slow the spread of multidrug-resistant Neisseria gonorrhoeae.Annals of the New York Academy of Sciences · 2019Review
- Heteroresistance to the model antimicrobial peptide polymyxin B in the emerging Neisseria meningitidis lineage 11.2 urethritis clade: mutations in the pilMNOPQ operon.Molecular microbiology · 2019Article
- Neisseria gonorrhoeae host adaptation and pathogenesis.Nature reviews. Microbiology · 2018Review
- The MtrCDE Efflux Pump Contributes to Survival ofFrontiers in microbiology · 2018Article
- A Case of Decreased Susceptibility to Ceftriaxone in Neisseria gonorrhoeae in the Absence of a Mosaic Penicillin-Binding Protein 2 (penA) Allele.Sexually transmitted diseases · 2017Article
- WGS to predict antibiotic MICs for Neisseria gonorrhoeae.The Journal of antimicrobial chemotherapy · 2017Article
- Susceptibility to ceftriaxone and occurrence of penicillinase plasmids in Neisseria gonorrhoeae strains isolated in Poland in 2012-2013.Folia microbiologica · 2016Article
- Novel Genes Related to Ceftriaxone Resistance Found among Ceftriaxone-Resistant Neisseria gonorrhoeae Strains Selected In Vitro.Antimicrobial agents and chemotherapy · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The penC resistance gene was previously characterized in an FA19 penA mtrR penB gonococcal strain (PR100) as a spontaneous mutation that increased resistance to penicillin and tetracycline. We show here that antibiotic resistance mediated by penC is the result of a Glu-666 to Lys missense mutation in the pilQ gene that interferes with the formation of the SDS-resistant high-molecular-mass PilQ secretin complex, disrupts piliation and decreases transformation frequency by 50-fold. Deletion of pilQ in PR100 confers the same level of antibiotic resistance as the penC mutation, but increased resistance was observed only in strains containing the mtrR and penB resistance determinants. Site-saturation mutagenesis of Glu-666 revealed that only acidic or amidated amino acids at this position preserved PilQ function. Consistent with early studies suggesting the importance of cysteine residues for stability of the PilQ multimer, mutation of either of the two cysteine residues in FA19 PilQ led to a similar phenotype as penC: increased antibiotic resistance, loss of piliation, intermediate levels of transformation competence and absence of SDS-resistant PilQ oligomers. These data show that a functional secretin complex can enhance the entry of antibiotics into the cell and suggest that the PilQ oligomer forms a pore in the outer membrane through which antibiotics diffuse into the periplasm.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.