A Novel 6′<i>-N-</i>Aminoglycoside Acetyltransferase, AAC(6′)-Ial, from a Clinical Isolate of<i>Serratia marcescens</i>

Tada, Tatsuya; Miyoshi‐Akiyama, Tohru; Shimada, Kayo; Dahal, Ranjan Kumar; Mishra, Shyam Kumar; Ohara, Hiroshi; Kirikae, Teruo; Pokhrel, Bharat Mani

doi:10.1089/mdr.2015.0126

Cited by 4 publications

(2 citation statements)

References 23 publications

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“…Heidelberg ancestral strains each carried chromosomally encoded aminoglycoside (aac (6')-Iy) and fosfomycin (fosA7) genes [54] that have been demonstrated to confer resistance to tobramycin, netilmicin, neomycin, amikacin, kanamycin and fosfomycin [55–57]. To assess the correlation between AMR and the acquisition of Col plasmids, we performed antibiotic susceptibility testing (AST) on evolved S .…”

Section: Resultsmentioning

confidence: 99%

Hotspot mutations and ColE1 plasmids contribute to the fitness of Salmonella Heidelberg in poultry litter

et al. 2018

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Salmonella enterica subsp. enterica serovar Heidelberg (S. Heidelberg) is a clinically-important serovar linked to food-borne illness, and commonly isolated from poultry. Investigations of a large, multistate outbreak in the USA in 2013 identified poultry litter (PL) as an important extra-intestinal environment that may have selected for specific S. Heidelberg strains. Poultry litter is a mixture of bedding materials and chicken excreta that contains chicken gastrointestinal (GI) bacteria, undigested feed, feathers, and other materials of chicken origin. In this study, we performed a series of controlled laboratory experiments which assessed the microevolution of two S. Heidelberg strains (SH-2813 and SH-116) in PL previously used to raise 3 flocks of broiler chickens. The strains are closely related at the chromosome level, differing from the reference genome by 109 and 89 single nucleotide polymorphisms/InDels, respectively. Whole genome sequencing was performed on 86 isolates recovered after 0, 1, 7 and 14 days of microevolution in PL. Only strains carrying an IncX1 (37kb), 2 ColE1 (4 and 6kb) and 1 ColpVC (2kb) plasmids survived more than 7 days in PL. Competition experiments showed that carriage of these plasmids was associated with increased fitness. This increased fitness was associated with an increased copy number of IncX1 and ColE1 plasmids. Further, all Col plasmid-bearing strains had hotspot mutations in 37 loci on the chromosome and in 3 loci on the IncX1 plasmid. Additionally, we observed a decrease in susceptibility to tobramycin, kanamycin, gentamicin, neomycin and fosfomycin for Col plasmid-bearing strains. Our study demonstrates how positive selection from poultry litter can change the evolutionary path of S. Heidelberg.

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Section: Resultsmentioning

confidence: 99%

Hotspot mutations and ColE1 plasmids contribute to the fitness of Salmonella Heidelberg in poultry litter

et al. 2018

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“… 1 A complete listing can be found in [ 26 ]; 2 The protein named AAC(6′)-Iap in [ 274 ] is named different in GenBank under the stated accession number. …”

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confidence: 99%

Amikacin: Uses, Resistance, and Prospects for Inhibition

2017

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Aminoglycosides are a group of antibiotics used since the 1940s to primarily treat a broad spectrum of bacterial infections. The primary resistance mechanism against these antibiotics is enzymatic modification by aminoglycoside-modifying enzymes that are divided into acetyl-transferases, phosphotransferases, and nucleotidyltransferases. To overcome this problem, new semisynthetic aminoglycosides were developed in the 70s. The most widely used semisynthetic aminoglycoside is amikacin, which is refractory to most aminoglycoside modifying enzymes. Amikacin was synthesized by acylation with the l-(−)-γ-amino-α-hydroxybutyryl side chain at the C-1 amino group of the deoxystreptamine moiety of kanamycin A. The main amikacin resistance mechanism found in the clinics is acetylation by the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib], an enzyme coded for by a gene found in integrons, transposons, plasmids, and chromosomes of Gram-negative bacteria. Numerous efforts are focused on finding strategies to neutralize the action of AAC(6′)-Ib and extend the useful life of amikacin. Small molecules as well as complexes ionophore-Zn+2 or Cu+2 were found to inhibit the acetylation reaction and induced phenotypic conversion to susceptibility in bacteria harboring the aac(6′)-Ib gene. A new semisynthetic aminoglycoside, plazomicin, is in advance stage of development and will contribute to renewed interest in this kind of antibiotics.

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Designing potential lead compounds targeting aminoglycoside N (6′)-acetyltransferase in Serratia marcescens: A drug discovery strategy

Prabhu,

Shankari,

Rajamanikandan

et al. 2024

International Journal of Biological Macromolecules

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A Novel 6′-N-Aminoglycoside Acetyltransferase, AAC(6′)-Ial, from a Clinical Isolate ofSerratia marcescens

Cited by 4 publications

References 23 publications

Hotspot mutations and ColE1 plasmids contribute to the fitness of Salmonella Heidelberg in poultry litter

Hotspot mutations and ColE1 plasmids contribute to the fitness of Salmonella Heidelberg in poultry litter

Amikacin: Uses, Resistance, and Prospects for Inhibition

Designing potential lead compounds targeting aminoglycoside N (6′)-acetyltransferase in Serratia marcescens: A drug discovery strategy

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