Diversity in Structural Consequences of <scp>M</scp>ex<scp>Z</scp> Mutations in <i><scp>P</scp>seudomonas aeruginosa</i>

Jahandideh, Samad

doi:10.1111/cbdd.12104

Cited by 15 publications

(8 citation statements)

References 29 publications

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“…In so-called agrZ mutants, the mexZ gene and its product are compromised by a number of nonspecific genetic events (e.g., indels and point mutations) (425, 439, 443, 446-448, 450, 457). In addition to mutations causing mexZ disruption, some generate single amino acid substitutions in the DNA-binding domain, the dimerization domain, or the structure of MexZ, abrogating its repressor activity (416,452,458,459). A second group of mutants, dubbed agrW1, was defined in line with various defects in ribosomal proteins such as L1 (436), L25 (460), L21 and L27 (461), or components of the Fmt bypass (methionyltRNA fMet formyltransferase FolD) (445) that ultimately affect protein synthesis.…”

Section: Pseudomonas Aeruginosamentioning

confidence: 99%

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

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SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

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Section: Pseudomonas Aeruginosamentioning

confidence: 99%

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

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“…In Gram-negative bacteria, intrinsic resistance is associated with the regulation of outer membrane proteins including porins and components of efflux pump systems. Porins typically control the diffusion of small metabolites including antibiotics, while efflux systems function via an energy-dependent mechanism to pump out unwanted toxic substances such as antibiotics through specific efflux pumps (Li et al, 2007 , 2008 ; Vila et al, 2007 ; Jahandideh, 2013 ; Morita et al, 2014 ; Alcalde-Rico et al, 2016 ). Thus, the behaviors of these outer membrane proteins provide characteristic features of Gram-negative bacteria in response to antibiotics.…”

Section: Introductionmentioning

confidence: 99%

Outer Membrane Proteins form Specific Patterns in Antibiotic-Resistant Edwardsiella tarda

Peng

Wang

et al. 2017

Front. Microbiol.

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Outer membrane proteins of Gram-negative bacteria play key roles in antibiotic resistance. However, it is unknown whether outer membrane proteins that respond to antibiotics behave in a specific manner. The present study specifically investigated the differentially expressed outer membrane proteins of an antibiotic-resistant bacterium, Edwardsiella tarda, a Gram-negative pathogen that can lead to unnecessary mass medication of antimicrobials and consequently resistance development in aquaculture and a spectrum of intestinal and extraintestinal diseases in humans. The comparison of a clinically isolated strain to the laboratory derived kanamycin-, tetracycline-, or chloramphenicol-resistant strains identified their respective outer membrane proteins expression patterns, which are distinct to each other. Similarly, the same approach was utilized to profile the patterns in double antibiotic-resistant bacteria. Surprisingly, one pattern is always dominant over the other as to these three antibiotics; the pattern of chloramphenicol is over tetracycline, which is over kanamycin. This type of pattern was also confirmed in clinically relevant multidrug-resistant bacteria. In addition, the presence of plasmid encoding antibiotic-resistant genes also alters the outer membrane protein profile in a similar manner. Our results demonstrate that bacteria adapt the antibiotic stress through the regulation of outer membrane proteins expression. And more importantly, different outer membrane protein profiles were required to cope with different antibiotics. This type of specific pattern provides the rationale for the development of novel strategy to design outer membrane protein arrays to identify diverse multidrug resistance profiles as biomarkers for clinical medication.

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“…In wildtype strains, MexZ binds to and represses the promoter of the mexXY operon (Matsuo et al, 2004). Various mutations in mexZ have been identified in clinical isolates displaying aminoglycoside resistance (Jahandideh, 2013;Guenard et al, 2014). Expression of mexXY is inducible by ribosome-targeting drugs (Matsuo et al, 2004;Jeannot et al, 2005), which is mediated by PA5471 (Morita et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

SuhB is a novel ribosome associated protein that regulates expression of MexXY by modulating ribosome stalling in Pseudomonas aeruginosa

Shi

Jin

Bian

et al. 2015

Molecular Microbiology

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SummaryTranslation elongation is modulated by various ribosome-binding proteins. Environmental stresses, such as starvation and antibiotics, can cause stalling of bacterial ribosomes, which may alter gene expression through a transcription or translation attenuation mechanism. In Pseudomonas aeruginosa, the expression of MexXY multidrug efflux system, which plays a significant role in resistance against aminoglycoside antibiotics, is controlled by a translation surveillance mechanism. Stalling of ribosome at the PA5471 leader peptide (PA5471.1) mRNA leads to transcription of PA5471, which subsequently up-regulates the expression of MexXY. In this study, we found that mutation in a suhB gene leads to decreased susceptibility to aminoglycosides. Transcriptomic analysis revealed an up-regulation of MexXY and PA5471, which were demonstrated to be responsible for the decreased susceptibility of the suhB mutant. We further demonstrated that PA5471.1 is essential for the up-regulation of PA5471 in the suhB mutant. Co-immunoprecipitation assay revealed an interaction between SuhB and ribosome, suggesting a role of SuhB in translation. Indeed, higher amount of PA5471.1 mRNA was found to associate with ribosome isolated from the suhB mutant, indicating increased ribosome stalling. Therefore, this study identified SuhB as a novel ribosome associated protein that is involved in modulating ribosome activity.

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Diversity in Structural Consequences of MexZ Mutations in Pseudomonas aeruginosa

Cited by 15 publications

References 29 publications

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

Outer Membrane Proteins form Specific Patterns in Antibiotic-Resistant Edwardsiella tarda

SuhB is a novel ribosome associated protein that regulates expression of MexXY by modulating ribosome stalling in Pseudomonas aeruginosa

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