Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes.

Shaw, K J; Rather, Philip N.; Hare, R S; Miller, George H.

doi:10.1128/mmbr.57.1.138-163.1993

Cited by 706 publications

(538 citation statements)

References 84 publications

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“…The Swedish [10] as well as the Danish CFPA isolates were negative for the plasmid-borne genes aac(6¢)-Ib and ant(4¢)-IIb and the chromosomal gene aph(3¢)-IIps, which specify aminoglycoside-modifying enzymes and confer resistance mainly to amikacin. The drug-modifying enzymes are encoded by genes that are often transmissible among organisms [20] and in very few cases are enzymatic mechanisms of aminoglycoside resistance combined with impermeability-type resistance (efflux-mediated resistance mechanism) [5].…”

Section: Resultsmentioning

confidence: 99%

Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients

Islam

Jalal

et al. 2009

Clinical Microbiology and Infection

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In total, 40 Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients were included in this study. Twenty of these were collected in 1994 and 1997, from six CF patients, and the rest were collected from different CF patients in 2000 and 2001. The relative expression of mRNA for the efflux pump protein MexY was determined by real-time PCR and correlated with susceptibilities to amikacin and tobramycin. The chromosomal genes mexZ, rplY, galU, PA5471 and nuoG, which were found to have a role in the gradual increase in MICs of aminoglycoside antibiotics in laboratory mutants of P. aeruginosa, were analysed. MexY mRNA overproduction was found in 17/20 isolates collected in 1994 and 1997, and was correlated with decreased susceptibility to aminoglycosides. Alteration of the MexXY-OprM efflux system has been the main mechanism of resistance to aminoglycoside antibiotics in CF P. aeruginosa isolates over the 3-year period. In several isolates, expression of the PA5471 gene product might have some effect on elevated MICs of aminoglycosides. Inactivation of rplY, galU and/or nuoG may explain the gradual increase in MICs of aminoglycosides in laboratory mutants but probably not in the CF environment, as rplY and galU were unaltered in all isolates, and nuoG was not expressed in only one isolate. No 16S rRNA A-site mutations were found in any of the four copies of the gene in 13 investigated isolates.

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Section: Resultsmentioning

confidence: 99%

Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients

Islam

Jalal

et al. 2009

Clinical Microbiology and Infection

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“…GmE1 was found to be related to three AAC(3)-III enzymes, all of which have identical resistance profiles and the genes of which have been cloned from Pseudomonas spp. (Shaw et al, 1993). It was also found to be more distantly related to a cluster of four AAC(3) enzymes encoded by genes from actinomycetes.…”

Section: Identification Of Antibiotic Resistance Genes and Phylogenetmentioning

confidence: 95%

Characterization of novel antibiotic resistance genes identified by functional metagenomics on soil samples

Torres-Cortés

Millán

Ramírez-Saad

et al. 2011

Environmental Microbiology

100

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The soil microbial community is highly complex and contains a high density of antibiotic-producing bacteria, making it a likely source of diverse antibiotic resistance determinants. We used functional metagenomics to search for antibiotic resistance genes in libraries generated from three different soil samples, containing 3.6 Gb of DNA in total. We identified 11 new antibiotic resistance genes: 3 conferring resistance to ampicillin, 2 to gentamicin, 2 to chloramphenicol and 4 to trimethoprim. One of the clones identified was a new trimethoprim resistance gene encoding a 26.8 kDa protein closely resembling unassigned reductases of the dihydrofolate reductase group. This protein, Tm8-3, conferred trimethoprim resistance in Escherichia coli and Sinorhizobium meliloti (γ- and α-proteobacteria respectively). We demonstrated that this gene encoded an enzyme with dihydrofolate reductase activity, with kinetic constants similar to other type I and II dihydrofolate reductases (K(m) of 8.9 µM for NADPH and 3.7 µM for dihydrofolate and IC(50) of 20 µM for trimethoprim). This is the first description of a new type of reductase conferring resistance to trimethoprim. Our results indicate that soil bacteria display a high level of genetic diversity and are a reservoir of antibiotic resistance genes, supporting the use of this approach for the discovery of novel enzymes with unexpected activities unpredictable from their amino acid sequences.

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“…The genes or protein responsible for a particular process are noted as boxes. Inhibition of protein synthesis, particularly in translational initiation (Pestka, 1977) Acquisition of aminoglycoside-inactivating enzymes (Shaw et al, 1993), mutational alteration of target structural gene rrs (Alangaden et al, 1998) or ribosomal protein (Finken et al, 1993) d-cycloserine (cyclic analogue of d-alanine)…”

Section: Tuberculosismentioning

confidence: 99%

Exploring the potential of endophytes from medicinal plants as sources of antimycobacterial compounds

Alvin

Miller

Neilan

2014

Microbiological Research

315

153

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Natural product drug discovery has regained interest due to low production costs, structural diversity, and multiple uses of active compounds to treat various diseases. Attention has been directed towards medicinal plants as these plants have been traditionally used for generations to treat symptoms of numerous diseases. It is established that plants harbour microorganisms, collectively known as endophytes. Exploring the as-yet untapped natural products from the endophytes increases the chances of finding novel compounds. The concept of natural products targeting microbial pathogens has been applied to isolate novel antimycobacterial compounds, and the rapid development of drug-resistant Mycobacterium tuberculosis has significantly increased the need for new treatments against this pathogen. It remains important to continuously screen for novel compounds from natural sources, particularly from rarely encountered microorganisms, such as the endophytes. This review focuses on bioprospecting for polyketides and small peptides exhibiting antituberculosis activity, although current treatments against tuberculosis are described. It is established that natural products from these structure classes are often biosynthesised by microorganisms. Therefore it is hypothesised that some bioactive polyketides and peptides originally isolated from plants are in fact produced by their endophytes. This is of interest for further endophyte natural product investigations.

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Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes.

Cited by 706 publications

References 84 publications

Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients

Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients

Characterization of novel antibiotic resistance genes identified by functional metagenomics on soil samples

Exploring the potential of endophytes from medicinal plants as sources of antimycobacterial compounds

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