Esterase D Is Essential for Protection of<i>Neisseria gonorrhoeae</i>against Nitrosative Stress and for Bacterial Growth during Interaction with Cervical Epithelial Cells

Potter, Adam J.; Kidd, Stephen P.; Edwards, Jennifer; Falsetta, Megan L.; Apicella, Michael A.; Jennings, Michael P.; McEwan, Alastair G.

doi:10.1086/599987

Cited by 20 publications

(35 citation statements)

References 14 publications

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“…The P value was Ͻ0.02 for the copA mutant under each condition assayed. against nitrosative stress (20,21). In contrast, biofilm formation in the copA mutant was essentially the same as that of wild-type gonococci, suggesting that copper ions do not enhance nitrosative stress under these conditions.…”

Section: Discussionmentioning

confidence: 85%

“…In earlier publications, we also showed that mutation of estD and trxB resulted in a greatly diminished ability of N. gonorrhoeae to form biofilms both on glass and over THCECs (20,21). Therefore, we evaluated biofilm formation by wild-type 1291 and 1291 copA after 2 days of growth under continuous flow (Table 1; see Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In women, gonococci are typ-ically associated with the cervical epithelium and are able to invade, survive, and replicate within these cells (4). We previously reported that inactivation of estD and trxB, two genes in the NmlR regulon, results in reduced survival of N. gonorrhoeae during challenge of cervical epithelial cells (20,21). To determine if copA is also important during cervical infection, we tested the ability of N. gonorrhoeae 1291 and 1291 copA to associate with, invade, and survive within pex cells.…”

Section: Resultsmentioning

confidence: 99%

“…We have observed that an estD mutant is sensitive to killing in vitro by nitrite and by GSNO (20), whereas a trxB mutant is sensitive to killing by an NO generator (21). These results led us to conclude that components of the NmlR regulon are involved in protection of N. gonorrhoeae against nitrosative stress, although their precise biochemical roles are still under investigation (16).…”

Section: Discussionmentioning

confidence: 97%

“…NmlR controls the expression of a small regulon comprised of nmlR itself (NGO0602), adhC-estD (NGO0601-NGO0600, encoding an alcohol dehydrogenase pseudogene and a thioesterase gene, respectively), trxB (NGO0580, encoding thioredoxin reductase), and copA (NGO0579, encoding a putative cationtransporting ATPase). In subsequent studies, we showed that a trxB mutant was sensitive to killing by NO, whereas an estD mutant was sensitive to killing by S-nitrosoglutathione (GSNO) and was unable to grow in liquid cultures in the presence of nitrite (20,21). Both mutants showed reduced abilities to form a biofilm on transformed human cervical epithelial cells (THCECs) and also to invade and survive within primary cervical epithelial (pex) cells.…”

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confidence: 99%

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Phenotypic Characterization of acopAMutant of Neisseria gonorrhoeae Identifies a Link between Copper and Nitrosative Stress

et al. 2012

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NGO0579 is annotated copA in the Neisseria gonorrhoeae chromosome, suggesting that it encodes a cation-transporting ATPase specific for copper ions. Compared to wild-type cells, a copA mutant was more sensitive to killing by copper ions but not to other transition metals. The mutant also accumulated a greater amount of copper, consistent with the predicted role of CopA as a copper efflux pump. The copA mutant showed a reduced ability to invade and survive within human cervical epithelial cells, although its ability to form a biofilm on the surface of these cells was not significantly different from that of the wild type. In the presence of copper, the copA mutant exhibited increased sensitivity to killing by nitrite or nitric oxide. Therefore, we concluded that copper ion efflux catalyzed by CopA is linked to the nitrosative stress defense system of Neisseria gonorrhoeae. These observations suggest that copper may exert its effects as an antibacterial agent in the innate immune system via an interaction with reactive nitrogen species.

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Section: Discussionmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

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Phenotypic Characterization of acopAMutant of Neisseria gonorrhoeae Identifies a Link between Copper and Nitrosative Stress

et al. 2012

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The Moraxella catarrhalis AdhC–FghA system is important for formaldehyde detoxification and protection against pulmonary clearance

Othman,

Elhosseiny,

Eltayeb

et al. 2024

Med Microbiol Immunol

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Multidrug-resistant clinical isolates of Moraxella catarrhalis have emerged, increasing the demand for the identification of new treatment and prevention strategies. A thorough understanding of how M. catarrhalis can establish an infection and respond to different stressors encountered in the host is crucial for new drug-target identification. Formaldehyde is a highly cytotoxic compound that can be produced endogenously as a by-product of metabolism and exogenously from environmental sources. Pathways responsible for formaldehyde detoxification are thus essential and are found in all domains of life. The current work investigated the role of the system consisting of the S-hydroxymethyl alcohol dehydrogenase (AdhC), a Zn-dependent class III alcohol dehydrogenase, and the S-formyl glutathione hydrolase (FghA) in the formaldehyde detoxification process in M. catarrhalis. Bioinformatics showed that the components of the system are conserved across the species and are highly similar to those of Streptococcus pneumoniae, which share the same biological niche. Isogenic mutants were constructed to study the function of the system in M. catarrhalis. A single fghA knockout mutant did not confer sensitivity to formaldehyde, while the adhC–fghA double mutant is formaldehyde-sensitive. In addition, both mutants were significantly cleared in a murine pulmonary model of infection as compared to the wild type, demonstrating the system’s importance for this pathogen’s virulence. The respective phenotypes were reversed upon the genetic complementation of the mutants. To date, this is the first study investigating the role of the AdhC–FghA system in formaldehyde detoxification and pathogenesis of M. catarrhalis.

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Novel Bacterial MerR-Like Regulators

McEwan¹,

Djoko²,

Chen³

et al. 2011

Advances in Microbial Physiology

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Esterase D Is Essential for Protection ofNeisseria gonorrhoeaeagainst Nitrosative Stress and for Bacterial Growth during Interaction with Cervical Epithelial Cells

Cited by 20 publications

References 14 publications

Phenotypic Characterization of acopAMutant of Neisseria gonorrhoeae Identifies a Link between Copper and Nitrosative Stress

Phenotypic Characterization of acopAMutant of Neisseria gonorrhoeae Identifies a Link between Copper and Nitrosative Stress

The Moraxella catarrhalis AdhC–FghA system is important for formaldehyde detoxification and protection against pulmonary clearance

Novel Bacterial MerR-Like Regulators

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