Nosocomial Spread of the Integron-Located veb-1--Like Cassette Encoding an Extended-Spectrum  -Lactamase in Pseudomonas aeruginosa in Thailand

Girlich, Delphine; Naas, Thierry; Leelaporn, Amornrut; Poirel, Laurent; Fennewald, Michael; Nordmann, Patrice

doi:10.1086/338786

Cited by 96 publications

(116 citation statements)

References 25 publications

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“…The M. smegmatis mc 2 155 arr gene product exhibits more than 50% identity to ADP ribosyltransferases from Streptomyces coelicolor, Pseudomonas aeruginosa (26), Klebsiella pneumoniae (1), E. coli, and other enterobacteria (6,7,15). In the enterobacteria, rifampin ribosylation, mediated by arr-2 gene cassettes, is a clinically important mechanism of drug resistance.…”

Section: Discussionmentioning

confidence: 99%

A Rifampin-Hypersensitive Mutant Reveals Differences between Strains of Mycobacterium smegmatis and Presence of a Novel Transposon, IS 1623

Alexander

Jones

Liu

2003

Antimicrob Agents Chemother

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Rifampin is a front-line antibiotic for the treatment of tuberculosis. Infections caused by rifampin-and multidrug-resistant Mycobacterium tuberculosis strains are difficult to treat and contribute to a poor clinical outcome. Rifampin resistance most often results from mutations in rpoB. However, some drug-resistant strains have rpoB alleles that encode the phenotype for susceptibility. Similarly, non-M. tuberculosis mycobacteria exhibit higher levels of baseline resistance to rifampin, despite the presence of rpoB alleles that encode the phenotype for susceptibility. To identify other genes involved in rifampin resistance, we generated a library of Mycobacterium smegmatis mc 2 155 transposon insertion mutants. Upon screening this library, we identified one mutant that was hypersensitive to rifampin. The transposon insertion was localized to the arr gene, which encodes rifampin ADP ribosyltransferase, an enzyme able to inactivate rifampin. Sequence analysis revealed differences in the arr alleles of M. smegmatis strain mc 2 155 and previously described strain DSM 43756. The arr region of strain mc 2 155 contains a second, partial copy of the arr gene plus a novel insertion sequence, IS1623.Mycobacterial infections, including tuberculosis (TB) and leprosy, are bacterial diseases of global importance. The World Health Organization estimates that the worldwide incidences of TB increased 0.4% in 2001, to 8.5 million new cases (28). Control of TB is complicated by its ease of transmission, difficulties in administering the long-course chemotherapy regimens, and the appearance of strains that are multidrug resistant (MDR), which is defined as resistance to the two front-line anti-TB drugs, isoniazid and rifampin. Rifampin is a broad-spectrum antibiotic that inhibits bacterial DNA-dependent RNA polymerase activity. Resistance to rifampin is most often caused by mutations in rpoB, which encodes the ␤ subunit of RNA polymerase (20,25). In rifampin-resistant clinical isolates of Mycobacterium tuberculosis, an estimated 96% of the rpoB mutations map to an 81-bp region (codons 507 to 533) near the middle of the gene (20). Mutations at codons 531, 526, and 516 are the most common (13). A variety of assays that detect these sequence polymorphisms have been developed (3, 23) and allow the rapid determination of the drug susceptibilities of clinical M. tuberculosis isolates. In addition, an estimated 90% of rifampin-resistant clinical isolates are also isoniazid resistant, such that rifampin resistance is a positive indicator of MDR TB. However, about 4% of rifampin-resistant clinical isolates of M. tuberculosis have no mutations in the 81-bp core region or elsewhere in the rpoB gene (3,8,14,20). In addition, some mycobacteria, particularly atypical mycobacteria, such as Mycobacterium smegmatis, Mycobacterium avium, and Mycobacterium intracellulare, are resistant to rifampin, even though they possess sensitive RNA polymerase (9,14,20). These findings indicate that other genes can contribute to rifampin resistance. To identify s...

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Section: Discussionmentioning

confidence: 99%

A Rifampin-Hypersensitive Mutant Reveals Differences between Strains of Mycobacterium smegmatis and Presence of a Novel Transposon, IS 1623

Alexander

Jones

Liu

2003

Antimicrob Agents Chemother

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“…While 5' conserved region of class 1 integron includes class 1 integrase gene encoding a site-specific integrase (intI) and recombination site, 3' conserved region includes sulI and qacEΔ1 genes [18]. Class 1 integrons have been reported in P. aeruginosa isolates [8,[19][20][21][22][23][24][25][26][27]. Organization of class 2 integrons is similar to the class 1 integrons and they are inserted in the Tn7 transposons family.…”

Section: Introductionmentioning

confidence: 99%

Screening of Class 1 and Class 2 Integrons in Clinical Isolates of Pseudomonas aeruginosa Collected from Seven Hospitals in Turkey: A Multicenter Study

Çiçek¹,

Saral²,

Düzgün³

et al. 2013

OJMM

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Pseudomonas aeruginosa is one of the leading nosocomial pathogens worldwide, and their infections are difficult to treat due to acquired resistance to many antibiotics. This study aimed to detect class 1 and 2 integrons and antibiotic susceptibility of clinical isolates of P. aeruginosa. Two hundred and five P. aeruginosa strains were collected from the seven general state hospitals in Turkey. They were characterized by antimicrobial susceptibility testing, screened for class 1 and class 2 integrons, and evaluated for the association between antibiotic resistance phenotypes and the presence of integrons. intI gene was amplified in 10 isolates (4.87%) by PCR and in seven isolates of them (70%) were found different gene cassettes. The aadA gene integrated into the class 1 integrons was most frequently found and it was followed by aac genes and bla OXA family genes. Sequence analysis of variable regions of the class 1 integrons showed five gene cassette arrays;

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“…The first reported VEB-type ESBL, VEB-1, was detected in Pseudomonas aeruginosa strains from Southeast Asia (22). Unlike most of the ESBL genes, bla VEB-1 is part of a gene cassette and is located in class 1 integrons of various structures (10,11,15,16). …”

mentioning

confidence: 99%

Outbreak of Infection Caused by Enterobacter cloacae Producing the Novel VEB-3 Beta-Lactamase in China

Jiang

et al. 2005

J Clin Microbiol

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ceftazidime-resistant or cefotaxime-resistant nonrepetitive Enterobacter cloacae isolates were collected from 27 patients hospitalized at HuaShan Hospital, Shanghai, People's Republic of China. The Etest did not detect extended-spectrum beta-lactamases (ESBLs) in those 27 isolates; however, screening by the NCCLS ESBL disk test and confirmatory tests detected ESBLs in 4 of 27 isolates and PCR detected ESBLs in 23 of 27 isolates. The majority of ESBL producers exhibited the same repetitive extragenic palindromic PCR pattern but harbored different ESBL genes. CTX-M-3 was the most prevalent ESBL in our study. Interestingly, 12 clonally related E. cloacae isolates possessed a novel bla VEB -type beta-lactamase, bla VEB-3 . Bla VEB-3 was encoded by the chromosome and was located in an integron. Nine of the 12 isolates harbored both the bla VEB-3 and the bla CTX-M-3 -like ESBLs. This is the first report of a VEB-1-like ESBL in China and the first report of the simultaneous presence of VEB-1 and CTX-M-3-like ESBLs in an isolate.Enterobacter cloacae is an important opportunistic pathogen known to cause nosocomial septicemia and urinary tract and respiratory tract infections (9, 25). Reports of multidrug-resistant isolates have increased during the last decade, probably as a result of the extensive use of broad-spectrum antibiotics. In some patient populations, the derepressed production of the AmpC beta-lactamase is a mechanism of beta-lactam resistance in E. cloacae strains (25,28). However, the occurrence of extended-spectrum beta-lactamases (ESBLs) in members of the family Enterobacteriaceae that possess inducible Bush group 1 chromosomal beta-lactamases is also increasingly reported worldwide (1,3,4,5,6,8,12).A 4-month survey was carried out to evaluate the prevalence of diverse ESBLs among E. cloacae isolates in HuaShan Hospital, Shanghai, People's Republic of China. This study identified a novel VEB-type ESBL, VEB-3. This is also the first report of VEB-1-like ESBLs from nosocomial isolates in the People's Republic of China. The first reported VEB-type ESBL, VEB-1, was detected in Pseudomonas aeruginosa strains from Southeast Asia (22). Unlike most of the ESBL genes, bla VEB-1 is part of a gene cassette and is located in class 1 integrons of various structures (10,11,15,16). MATERIALS AND METHODSBacterial isolates. Twenty-seven nonrepetitive ceftazidime-resistant or cefotaxime-resistant E. cloacae clinical isolates were consecutively collected in the bacteriology laboratory of the Center of Laboratory Medicine, Huashan Hospital, Shanghai, from November 2002 to February 2003. During this period, 58 isolates of the species were obtained from patient specimens (22 from sputum, 22 from urine, 6 from blood, and 8 from other specimens). The isolates were identified with the API 20E system (bioMerieux SA, Marcy-1ЈEtoile, France). Escherichia coli ATCC 25922 was used as a negative control. Klebsiella pneumoniae ATCC 700603 was used as an ESBL-positive control. E. cloacae 029 and E. cloacae 029 M were used as control strai...

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Nosocomial Spread of the Integron-Located veb-1--Like Cassette Encoding an Extended-Spectrum -Lactamase in Pseudomonas aeruginosa in Thailand

Cited by 96 publications

References 25 publications

A Rifampin-Hypersensitive Mutant Reveals Differences between Strains of Mycobacterium smegmatis and Presence of a Novel Transposon, IS 1623

A Rifampin-Hypersensitive Mutant Reveals Differences between Strains of Mycobacterium smegmatis and Presence of a Novel Transposon, IS 1623

Screening of Class 1 and Class 2 Integrons in Clinical Isolates of Pseudomonas aeruginosa Collected from Seven Hospitals in Turkey: A Multicenter Study

Outbreak of Infection Caused by Enterobacter cloacae Producing the Novel VEB-3 Beta-Lactamase in China

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