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The phase-variable allele of the pilus glycosylation gene pglA is not strongly associated with strains of Neisseria gonorrhoeae isolated from patients with disseminated gonococcal infection.

ABSTRACT: The Neisseria gonorrhoeae pglA gene has two alleles, one of which is phase variable. A previous study reported that all disseminated gonococcal infection (DGI) isolates contained the phase-variable allele and proposed a causal link. In the present study of 81 strains no absolute correlation between DGI and the phase-variable pglA allele was observed.

SUBMITTER: Power PM

PROVIDER: S-EPMC1932893 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

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The phase-variable allele of the pilus glycosylation gene pglA is not strongly associated with strains of Neisseria gonorrhoeae isolated from patients with disseminated gonococcal infection.

Power P M PM Ku S C SC Rutter K K Warren M J MJ Limnios E A EA Tapsall J W JW Jennings M P MP

Infection and immunity 20070212 6

The Neisseria gonorrhoeae pglA gene has two alleles, one of which is phase variable. A previous study reported that all disseminated gonococcal infection (DGI) isolates contained the phase-variable allele and proposed a causal link. In the present study of 81 strains no absolute correlation between DGI and the phase-variable pglA allele was observed. ...[more]

PMID: 17296763

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Project description:The six-component maintenance of lipid asymmetry (Mla) system is responsible for retrograde transport of phospholipids, ensuring the barrier function of the Gram-negative cell envelope. Located within the outer membrane, MlaA (VacJ) acts as a channel to shuttle phospholipids from the outer leaflet. We identified Neisseria gonorrhoeae MlaA (ngo2121) during high-throughput proteomic mining for potential therapeutic targets against this medically important human pathogen. Our follow-up phenotypic microarrays revealed that lack of MlaA results in a complex sensitivity phenome. Herein we focused on MlaA function in cell envelope biogenesis and pathogenesis. We demonstrate the existence of two MlaA classes among 21 bacterial species, characterized by the presence or lack of a lipoprotein signal peptide. Purified truncated N. gonorrhoeae MlaA elicited antibodies that cross-reacted with a panel of different Neisseria. Little is known about MlaA expression; we provide the first evidence that MlaA levels increase in stationary phase and under anaerobiosis but decrease during iron starvation. Lack of MlaA resulted in higher cell counts during conditions mimicking different host niches; however, it also significantly decreased colony size. Antimicrobial peptides such as polymyxin B exacerbated the size difference while human defensin was detrimental to mutant viability. Consistent with the proposed role of MlaA in vesicle biogenesis, the ΔmlaA mutant released 1.7-fold more membrane vesicles. Comparative proteomics of cell envelopes and native membrane vesicles derived from ΔmlaA and wild type bacteria revealed enrichment of TadA-which recodes proteins through mRNA editing-as well as increased levels of adhesins and virulence factors. MlaA-deficient gonococci significantly outcompeted (up to 16-fold) wild-type bacteria in the murine lower genital tract, suggesting the growth advantage or increased expression of virulence factors afforded by inactivation of mlaA is advantageous in vivo. Based on these results, we propose N. gonorrhoeae restricts MlaA levels to modulate cell envelope homeostasis and fine-tune virulence.

Dataset Information

The phase-variable allele of the pilus glycosylation gene pglA is not strongly associated with strains of Neisseria gonorrhoeae isolated from patients with disseminated gonococcal infection.

Publications

The phase-variable allele of the pilus glycosylation gene pglA is not strongly associated with strains of Neisseria gonorrhoeae isolated from patients with disseminated gonococcal infection.

Similar Datasets

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