Outer membrane porin M35 of Moraxella catarrhalis mediates susceptibility to aminopenicillins

Jetter, Marion; Heiniger, Nadja; Spaniol, Violeta; Troller, Rolf; Schaller, André; Aebi, Christoph

doi:10.1186/1471-2180-9-188

Cited by 13 publications

(18 citation statements)

References 63 publications

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“…in more than 90% of clinical isolates. 2 One study reported a significant increase in MIC for ampicillin and amoxicillin in M35 porin-deficient mutants, 24 which suggests that this porin affects outer membrane permeability for aminopenicillins in a clinically relevant manner.…”

Section: Disscussionmentioning

confidence: 99%

Antimicrobial resistance of Moraxella catarrhalis isolates in Taiwan

Hsu

Lin

Chen

et al. 2012

Journal of Microbiology, Immunology and Infection

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The rates of resistance to cefaclor, cefuroxime, tetracycline and SXT are now increasing in Taiwan. Molecular typing showed that at least two closely related BRO-1 clones are circulating. Although amoxicillin + clavulanate remains the antimicrobial therapy of choice for M. catarrhalis infections, continued surveillance of antimicrobial susceptibility and application of control measures against further transmission are required to inhibit the emergence of the resistant strains.

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Section: Disscussionmentioning

confidence: 99%

Antimicrobial resistance of Moraxella catarrhalis isolates in Taiwan

Hsu

Lin

Chen

et al. 2012

Journal of Microbiology, Immunology and Infection

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“…20 We studied 52 middle ear isolates obtained from Prof. Ron Dagan (Beer-Sheva, Israel). PCR resulted in positive products for all 52 strains.…”

Section: Resultsmentioning

confidence: 99%

“…20 To verify these findings in vivo and clarify its clinical relevance regarding amoxicillin therapy of acute otitis media caused by M. catarrhalis , further analyses will be needed. In particular, it will be necessary to elucidate whether down-regulation of M35 during treatment may contribute to treatment failure caused by isolates that have been shown to be susceptible in vitro .…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of porin M35 in Moraxella catarrhalis by aminopenicillins and environmental factors and its potential contribution to the mechanism of resistance to aminopenicillins

Jetter¹,

Spaniol²,

Troller³

et al. 2010

Journal of Antimicrobial Chemotherapy

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ObjectivesThe outer membrane protein M35 of Moraxella catarrhalis is an antigenically conserved porin. Knocking out M35 significantly increases the MICs of aminopenicillins. The aim of this study was to determine the biological mechanism of this potentially new antimicrobial resistance mechanism of M. catarrhalis and the behaviour of M35 in general stress situations.MethodsPCR using m35-specific primers was used to detect the m35 gene in clinical isolates. The m35 mRNA expression of strains 300, O35E and 415 after exposure to amoxicillin and different stress conditions was measured by real-time PCR and normalized in relation to their 16S rRNA expression. The expression of M35 protein was analysed by SDS-PAGE and western blotting.ResultsScreening of 52 middle ear isolates resulted in positive PCR products for all tested strains. The analysis of m35 mRNA expression after amoxicillin treatment showed 24%–85% down-regulation compared with the respective amoxicillin-free controls in all three strains tested. Also, analysis of protein concentrations revealed lower M35 expression after growth with amoxicillin. Investigation of M35 during general stress responses showed down-regulation of the porin with growth at 26°C and 42°C, under hyperosmolar stress and under iron restriction.ConclusionsThe reduced expression of M35 after aminopenicillin exposure indicates a novel resistance mechanism against aminopenicillins in M. catarrhalis, which may be relevant in vivo. The differences in expression after different stress treatments demonstrate that M35 is involved in general stress responses.

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“…The Opp system of M. catarrhalis is essential for mediating uptake of peptides between 5 and 10 aa residues in length, yet peptides of smaller or larger size were not dependent on the Opp system for uptake. We speculate that smaller and larger peptides are being imported by other mechanisms, such as the general porin complex in the case of small peptides or through an uptake system that has not yet been characterized (58). An alternative explanation for the larger peptides is that they may undergo proteolytic degradation in the periplasm by any number of annotated peptidase enzymes present in the genome of M. catarrhalis that have not been characterized (38,59,60).…”

Section: Discussionmentioning

confidence: 99%

Role of the Oligopeptide Permease ABC Transporter of Moraxella catarrhalis in Nutrient Acquisition and Persistence in the Respiratory Tract

et al. 2014

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Moraxella catarrhalis is a strict human pathogen that causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults, resulting in significant worldwide morbidity and mortality. M. catarrhalis has a growth requirement for arginine; thus, acquiring arginine is important for fitness and survival. M. catarrhalis has a putative oligopeptide permease ABC transport operon (opp) consisting of five genes (oppB, oppC, oppD, oppF, and oppA), encoding two permeases, two ATPases, and a substrate binding protein. Thermal shift assays showed that the purified recombinant substrate binding protein OppA binds to peptides 3 to 16 amino acid residues in length regardless of the amino acid composition. A mutant in which the oppBCDFA gene cluster is knocked out showed impaired growth in minimal medium where the only source of arginine came from a peptide 5 to 10 amino acid residues in length. Whether methylated arginine supports growth of M. catarrhalis is important in understanding fitness in the respiratory tract because methylated arginine is abundant in host tissues. No growth of wildtype M. catarrhalis was observed in minimal medium in which arginine was present only in methylated form, indicating that the bacterium requires L-arginine. An oppA knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the Opp system mediates both uptake of peptides and fitness in the respiratory tract. Moraxella catarrhalis, a Gram-negative diplococcus, is a commensal of the upper respiratory tract, as well as a humanspecific pathogen responsible for 10 to 20% of otitis media in children and approximately 10% of exacerbations of chronic obstructive pulmonary disease (COPD) in adults in the United States (1-6). Otitis media is the most common reason for pediatric office visits and the prescribing of antibiotics to children, typically by the age of 3 years (7-12). COPD is the third leading cause of death in the United States, affecting at least 24 million people, and costs $50 billion in health care expenses each year (13-16). COPD is considered a major unmet medical need that is increasing in prevalence throughout the world (17, 18). Antibiotic resistance is an additional concern, with nearly 100% of clinical isolates of M. catarrhalis displaying resistance to ␤-lactam drugs with the ability to protect other ␤-lactam-sensitive bacteria in the surrounding environment (3, 9, 19-23).In the last 2 decades, M. catarrhalis has transitioned from being considered an emerging to an established pathogen. Since this bacterium was previously considered to be a commensal, the literature on mechanisms that allow M. catarrhalis to thrive in the harsh environment of the human respiratory tract is sparse, and the associated virulence mechanisms are not well studied (1, 2, 24-29). There is a need to understand bacterial physiology and metabolism during infection as these pathways and traits could be exploited f...

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Outer membrane porin M35 of Moraxella catarrhalis mediates susceptibility to aminopenicillins

Cited by 13 publications

References 63 publications

Antimicrobial resistance of Moraxella catarrhalis isolates in Taiwan

Antimicrobial resistance of Moraxella catarrhalis isolates in Taiwan

Down-regulation of porin M35 in Moraxella catarrhalis by aminopenicillins and environmental factors and its potential contribution to the mechanism of resistance to aminopenicillins

Role of the Oligopeptide Permease ABC Transporter of Moraxella catarrhalis in Nutrient Acquisition and Persistence in the Respiratory Tract

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