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            -Alanine Modification of a Protease-Susceptible Outer Membrane Component by the Bordetella pertussis
            <i>dra</i>
            Locus Promotes Resistance to Antimicrobial Peptides and Polymorphonuclear Leukocyte-Mediated Killing

Taneja, Neetu Kumra; Ganguly, Tridib; Nelson, Kimberly; Dubey, Purnima; Poole, Leslie B.; Deora, Rajendar

doi:10.1128/jb.00510-13

Cited by 23 publications

(17 citation statements)

References 59 publications

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“…To determine the relative surface charge, overnight cultures were washed twice with HEPES buffer (20 mM, pH 7.25) and resuspended to an OD 578 of 0.1. fluorescein isothiocyanate (FITC)-poly-L-lysine (FPLL) was added to a final concentration of 5 g/ ml, and the percentage of bound FPLL was determined as described previously (33,34).…”

Section: Methodsmentioning

confidence: 99%

Daptomycin Tolerance in the Staphylococcus aureus pitA6 Mutant Is Due to Upregulation of the dlt Operon

Mechler

Bonetti

Reichert

et al. 2016

Antimicrob Agents Chemother

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dUnderstanding the mechanisms of how bacteria become tolerant toward antibiotics during clinical therapy is a very important object. In a previous study, we showed that increased daptomycin (DAP) tolerance of Staphylococcus aureus was due to a point mutation in pitA (inorganic phosphate transporter) that led to intracellular accumulation of both inorganic phosphate (P i ) and polyphosphate (polyP). DAP tolerance in the pitA6 mutant differs from classical resistance mechanisms since there is no increase in the MIC. In this follow-up study, we demonstrate that DAP tolerance in the pitA6 mutant is not triggered by the accumulation of polyP. Transcriptome analysis revealed that 234 genes were at least 2.0-fold differentially expressed in the mutant. Particularly, genes involved in protein biosynthesis, carbohydrate and lipid metabolism, and replication and maintenance of DNA were downregulated. However, the most important change was the upregulation of the dlt operon, which is induced by the accumulation of intracellular P i . The GraXRS system, known as an activator of the dlt operon (D-alanylation of teichoic acids) and of the mprF gene (multiple peptide resistance factor), is not involved in DAP tolerance of the pitA6 mutant. In conclusion, DAP tolerance of the pitA6 mutant is due to an upregulation of the dlt operon, triggered directly or indirectly by the accumulation of P i .

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Section: Methodsmentioning

confidence: 99%

Daptomycin Tolerance in the Staphylococcus aureus pitA6 Mutant Is Due to Upregulation of the dlt Operon

Mechler

Bonetti

Reichert

et al. 2016

Antimicrob Agents Chemother

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“…pertussis shows a range of susceptibility to numerous CAMPs (7), and porcine beta-defensin 1 (pBD1) protects against B. pertussis infection in a newborn piglet model, demonstrating the protective capability of CAMPs against this pathogen (8). Recently, an LPS-independent mechanism in B. pertussis was also shown to increase CAMP resistance (9). B. pertussis has thus evolved at least two separate mechanisms for CAMP resistance, suggesting that this strategy plays an important role in the survival of this human-restricted pathogen.…”

mentioning

confidence: 99%

Bordetella pertussis Lipid A Glucosamine Modification Confers Resistance to Cationic Antimicrobial Peptides and Increases Resistance to Outer Membrane Perturbation

Shah

Hancock

Fernandez

2014

Antimicrob Agents Chemother

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Bordetella pertussis, the causative agent of whooping cough, has many strategies for evading the human immune system. Lipopolysaccharide (LPS) is an important Gram-negative bacterial surface structure that activates the immune system via Toll-like receptor 4 and enables susceptibility to cationic antimicrobial peptides (CAMPs). We show modification of the lipid A region of LPS with glucosamine increased resistance to numerous CAMPs, including LL-37. Furthermore, we demonstrate that this glucosamine modification increased resistance to outer membrane perturbation.

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“…The activated amino acid, which is alanine in Gram-positive bacteria, has not been conclusively determined in Gram-negative bacteria. It has been suggested that it might also be alanine in B. pertussis (14). However, in V. cholerae, a group of three alm genes confers resistance to AMPs by adding glycine to LPS.…”

Section: Discussionmentioning

confidence: 99%

“…The third V. cholerae protein required to add glycine to LPS, AlmG, is also an inner-membrane protein, but it has no homology with DltB, suggesting that there is a different target or mechanism for modifying its substrate (4). A mutant with deletion of the four B. pertussis dra (dlt) genes shows an increased sensitivity to AMP, but a specific role of the individual genes has not been tested (14). The function of DltD is unknown, even in Gram-positive bacteria.…”

Section: Discussionmentioning

confidence: 99%

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Antimicrobial Peptide Resistance Genes in the Plant Pathogen Dickeya dadantii

Pandin

Caroff

Condemine

2016

Appl Environ Microbiol

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Modification of teichoic acid through the incorporation of D-alanine confers resistance in Gram-positive bacteria to antimicrobial peptides (AMPs). This process involves the products of the dltXABCD genes. These genes are widespread in Gram-positive bacteria, and they are also found in a few Gram-negative bacteria. Notably, these genes are present in all soft-rot enterobacteria (Pectobacterium and Dickeya) whose dltDXBAC operons have been sequenced. We studied the function and regulation of these genes in Dickeya dadantii. dltB expression was induced in the presence of the AMP polymyxin. It was not regulated by PhoP, which controls the expression of some genes involved in AMP resistance, but was regulated by ArcA, which has been identified as an activator of genes involved in AMP resistance. However, arcA was not the regulator responsible for polymyxin induction of these genes in this bacterium, which underlines the complexity of the mechanisms controlling AMP resistance in D. dadantii. Two other genes involved in resistance to AMPs have also been characterized, phoS and phoH. dltB, phoS, phoH, and arcA but not dltD mutants were more sensitive to polymyxin than the wild-type strain. Decreased fitness of the dltB, phoS, and phoH mutants in chicory leaves indicates that their products are important for resistance to plant AMPs. IMPORTANCE Gram-negative bacteria can modify their lipopolysaccharides (LPSs) to resist antimicrobial peptides (AMPs). Soft-rot enterobacteria (Dickeya and Pectobacterium spp.) possess homologues of the dlt genes in their genomes which, in Gram-positive bacteria, are involved in resistance to AMPs. In this study, we show that these genes confer resistance to AMPs, probably by modifying LPSs, and that they are required for the fitness of the bacteria during plant infection. Two other new genes involved in resistance were also analyzed. These results show that bacterial resistance to AMPs can occur in bacteria through many different mechanisms that need to be characterized.

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d -Alanine Modification of a Protease-Susceptible Outer Membrane Component by the Bordetella pertussis dra Locus Promotes Resistance to Antimicrobial Peptides and Polymorphonuclear Leukocyte-Mediated Killing

Cited by 23 publications

References 59 publications

Daptomycin Tolerance in the Staphylococcus aureus pitA6 Mutant Is Due to Upregulation of the dlt Operon

Daptomycin Tolerance in the Staphylococcus aureus pitA6 Mutant Is Due to Upregulation of the dlt Operon

Bordetella pertussis Lipid A Glucosamine Modification Confers Resistance to Cationic Antimicrobial Peptides and Increases Resistance to Outer Membrane Perturbation

Antimicrobial Peptide Resistance Genes in the Plant Pathogen Dickeya dadantii

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