A Conservative Amino Acid Mutation in the Chromosome‐Encoded Dihydrofolate Reductase Confers Trimethoprim Resistance in<i>Streptococcus pneumoniae</i>

Pikis, Andreas; Donkersloot, Jacob A.; Rodríguez, William J.; Keith, Jerry M.

doi:10.1086/515371

Cited by 71 publications

(47 citation statements)

References 45 publications

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“…aureus (Huovinen 2001) and Strep. pneumoniae (Pikis et al 1998). Similarly, mutations in the chromosomal dhps (dihydropteroate synthetase) gene are prevalent in nature.…”

Section: Resultsmentioning

confidence: 99%

Bacteriological Study of Wound Infection and Antibiotic Susceptibility Pattern of the Isolates

Shrestha

2014

Nepal Journal of Science and Technology

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Wound infections result in sepsis, limb loss, long hospital stays, higher costs, and are responsible for significant human mortality and morbidity worldwide. The present study was conducted to isolate and identify the causative organisms of wound infection, to determine the antibiotic susceptibility pattern of the isolates and to study the risk factors for wound infection. The study was conducted for six months in which pus specimens collected from 244 patients were processed to investigate etiological agents using standard technique. Disc susceptibility of bacterial agents were then determined. A total of 244 pus samples were collected and 147 (60.20%) samples showed growth. A total of 150 bacterial isolates were isolated; of which 118 (78.67%) were Gram positive and 32 (21.33%) were Gram negative bacteria. Staphylococcus aureus (72.00%) was most common followed by Escherichia coli (6.67%), Citrobacter freundii (5.34%), Staphylococcus epidermidis (4.00%), Pseudomonas aeruginosa (3.33%), Proteus mirabilis (2.00%), Enterococcus faecalis (1.33%), Acinetobacter spp. (1.33%), Klebsiella oxytoca (1.33%), Klebsiella pneumoniae (1.33%), Streptococcus pneumoniae (0.67%) and Streptococcus pyogenes (0.67%). The most effective antibiotic for Gram positive isolates was Gentamicin (77.97%). For Gram negative isolates (except Ps. aeruginosa), Amikacin (74.07%), for Ps. aeruginosa, Amikacin, Ciprofloxacin, Gentamicin and Ofloxacin each with the susceptibility of 80.00% and for Staph. aureus, Cloxacillin (79.63%) were the most effective antibiotics. Hence, the most common isolate in wound infection was Staph. aureus followed by E. coli. Therefore, routine microbiological analysis of the wound specimens and their antibiotic susceptibility testing is recommended that will guide clinician for treatment of wound infection.

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“…aureus (Huovinen 2001) and Strep. pneumoniae (Pikis et al 1998). Similarly, mutations in the chromosomal dhps (dihydropteroate synthetase) gene are prevalent in nature.…”

Section: Resultsmentioning

confidence: 99%

Bacteriological Study of Wound Infection and Antibiotic Susceptibility Pattern of the Isolates

Shrestha

2014

Nepal Journal of Science and Technology

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“…There were two substitutions in DHFR (FolA) in Bp1651 TR70_1420, I99L and A145T, in comparison to three other strains. The I99L substitution at the equivalent position occurs in trimethoprimresistant Streptococcus pneumoniae (I100L) and is sufficient to confer trimethoprim resistance in that species (56)(57)(58). This substitution is localized to the predicted active site of the DHFR enzymes (59) and may therefore be responsible for trimethoprim resistance in B. pseudomallei.…”

Section: Figmentioning

confidence: 99%

Antibiotic Resistance Markers in Burkholderia pseudomallei Strain Bp1651 Identified by Genome Sequence Analysis

Bugrysheva

Sue

Gee

et al. 2017

Antimicrob Agents Chemother

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Burkholderia pseudomallei Bp1651 is resistant to several classes of antibiotics that are usually effective for treatment of melioidosis, including tetracyclines, sulfonamides, and ␤-lactams such as penicillins (amoxicillin-clavulanic acid), cephalosporins (ceftazidime), and carbapenems (imipenem and meropenem). We sequenced, assembled, and annotated the Bp1651 genome and analyzed the sequence using comparative genomic analyses with susceptible strains, keyword searches of the annotation, publicly available antimicrobial resistance prediction tools, and published reports. More than 100 genes in the Bp1651 sequence were identified as potentially contributing to antimicrobial resistance. Most notably, we identified three previously uncharacterized point mutations in penA, which codes for a class A ␤-lactamase and was previously implicated in resistance to ␤-lactam antibiotics. The mutations result in amino acid changes T147A, D240G, and V261I. When individually introduced into select agent-excluded B. pseudomallei strain Bp82, D240G was found to contribute to ceftazidime resistance and T147A contributed to amoxicillin-clavulanic acid and imipenem resistance. This study provides the first evidence that mutations in penA may alter susceptibility to carbapenems in B. pseudomallei. Another mutation of interest was a point mutation affecting the dihydrofolate reductase gene folA, which likely explains the trimethoprim resistance of this strain. Bp1651 was susceptible to aminoglycosides likely because of a frameshift in the amrB gene, the transporter subunit of the AmrAB-OprA efflux pump. These findings expand the role of penA to include resistance to carbapenems and may assist in the development of molecular diagnostics that predict antimicrobial resistance and provide guidance for treatment of melioidosis.

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“…3A). From mid-log phase (A 660 of 0.2), the increase in cell mass would lead to increased production of H 2 (29), and their deduced amino acid sequences showed 75.4 and 57.1% identity, respectively, with that of S. mutans Dpr. To date, nonheme peroxidases (30, 31), a pseudocatalase (20), and oxidases (2, 10, 16, 34) of lactic acid bacteria, including streptococci, have been reported to substitute for catalase, which is present in other aerotolerant bacteria but not lactic acid bacteria, and some of them, including SOD, were proven to play a role in aerotolerance (9,10,21,27,33).…”

Section: Identification Of a Peroxide Resistance Gene From S Mutansmentioning

confidence: 99%

Role of the dpr Product in Oxygen Tolerance in Streptococcus mutans

et al. 2000

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We have previously identified and characterized the alkyl hydroperoxide reductase of Streptococcus mutans, which consists of two components, Nox-1 and AhpC. Deletion of both nox-1 and ahpC had no effect on the sensitivity of S. mutans to cumene hydroperoxide or H 2 O 2 , implying that the existence of another antioxidant system(s) independent of the Nox-1-AhpC system compensates for the deficiency. Here, a new antioxidant gene (dpr for Dps-like peroxide resistance gene) was isolated from the S. mutans chromosome by its ability to complement an ahpCF deletion mutant of Escherichia coli with a tert-butyl hydroperoxide-hypersensitive phenotype. The dpr gene complemented the defect in peroxidase activity caused by the deletion of nox-1 and ahpC in S. mutans. Under aerobic conditions, the dpr disruption mutant carrying a spectinomycin resistance gene (dpr::Spc r mutant) grew as well as wild-type S. mutans in liquid medium. However, the dpr::Spc r mutant could not form colonies on an agar plate under air. In addition, neither the dpr::Spc r ahpC::Em r ::nox-1 triple mutant nor the dpr::Spc r sod::Em r double mutant was able to grow aerobically in liquid medium. The 20-kDa dpr gene product Dpr is an iron-binding protein. Synthesis of Dpr was induced by exposure of S. mutans cells to air. We propose a mechanism by which Dpr confers aerotolerance on S. mutans.Bacteria contain certain enzymes capable of reacting with oxygen, and they cannot avoid confronting harmful reactive oxygen species, including superoxide anion (O 2 Ϫ ), hydrogen peroxide (H 2 O 2 ), and organic hydroperoxide, if they are exposed to air. To live in the presence of oxygen, they have to convert these reactive oxygen species to nontoxic molecules. Therefore, enzymes such as superoxide dismutases (SOD), catalases, and peroxidases are ubiquitously distributed in aerotolerant bacteria.Lactic acid bacteria, including Streptococcus mutans, lack cytochromes and other heme-containing proteins. Most lactic acid bacteria, except several lactobacilli which acquire catalase activity if a source of heme is added to their growth medium (42), also lack catalase. However, they can grow in the presence of air. In view of the defense against oxygen toxicity, the lack of catalase in lactic acid bacteria is inconsistent with their aerotolerance. Mechanisms by which lactic acid bacteria cope with peroxide-mediated stress are therefore an area under active investigation. We previously identified H 2 O 2 -forming NADH oxidase (Nox-1) in S. mutans and found that Nox-1 is homologous with a flavoprotein component, AhpF, of Salmonella typhimurium alkyl hydroperoxide reductase (AhpR), consisting of AhpF and AhpC (16,17,30). We also identified ahpC, which is homologous with ahpC of S. typhimurium, upstream of nox-1 in S. mutans (30). Analyses of purified AhpC together with Nox-1 have verified that these proteins act as a bicomponent peroxidase system in S. mutans, catalyzing the NADH-dependent reduction of organic hydroperoxides or H 2 O 2 to their respective alcohols and/or H 2 ...

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A Conservative Amino Acid Mutation in the Chromosome‐Encoded Dihydrofolate Reductase Confers Trimethoprim Resistance inStreptococcus pneumoniae

Cited by 71 publications

References 45 publications

Bacteriological Study of Wound Infection and Antibiotic Susceptibility Pattern of the Isolates

Bacteriological Study of Wound Infection and Antibiotic Susceptibility Pattern of the Isolates

Antibiotic Resistance Markers in Burkholderia pseudomallei Strain Bp1651 Identified by Genome Sequence Analysis

Role of the dpr Product in Oxygen Tolerance in Streptococcus mutans

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