Genetic and Functional Characterization of
 bla
 CTX-M-199
 , a Novel Tazobactam and Sulbactam Resistance-Encoding Gene Located in a Conjugative
 mcr-1
 -Bearing IncI2 Plasmid

Cai, Jiachang; Cheng, Qipeng; Shen, Yingbo; Gu, Danxia; Fang, Ying; Chan, Edward Wai Chi; Chen, Sheng

doi:10.1128/aac.00562-17

Cited by 19 publications

(24 citation statements)

References 13 publications

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“…In addition to the widespread presence of bla NDM on the Indian subcontinent, NDM now appears to be endemic to the Balkan countries, Northern Africa, and the Arabian Peninsula, where these countries may serve as a secondary reservoir for the enzyme (306). Recent outbreaks caused by NDM-producing Enterobacteriaceae have been reported in hospitals in Greece, Mexico, and the Netherlands and in a neonatal unit in China (311)(312)(313). Unlike the dissemination of KPC, high-risk clones and epidemic plasmids have not been widely implicated in the global spread of bla NDM genes (209).…”

Section: Carbapenemase-producing Bacteriamentioning

confidence: 99%

Epidemiology of β-Lactamase-Producing Pathogens

Bush

Bradford²

2020

Clin Microbiol Rev

572

440

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SUMMARY β-Lactam antibiotics have been widely used as therapeutic agents for the past 70 years, resulting in emergence of an abundance of β-lactam-inactivating β-lactamases. Although penicillinases in Staphylococcus aureus challenged the initial uses of penicillin, β-lactamases are most important in Gram-negative bacteria, particularly in enteric and nonfermentative pathogens, where collectively they confer resistance to all β-lactam-containing antibiotics. Critical β-lactamases are those enzymes whose genes are encoded on mobile elements that are transferable among species. Major β-lactamase families include plasmid-mediated extended-spectrum β-lactamases (ESBLs), AmpC cephalosporinases, and carbapenemases now appearing globally, with geographic preferences for specific variants. CTX-M enzymes include the most common ESBLs that are prevalent in all areas of the world. In contrast, KPC serine carbapenemases are present more frequently in the Americas, the Mediterranean countries, and China, whereas NDM metallo-β-lactamases are more prevalent in the Indian subcontinent and Eastern Europe. As selective pressure from β-lactam use continues, multiple β-lactamases per organism are increasingly common, including pathogens carrying three different carbapenemase genes. These organisms may be spread throughout health care facilities as well as in the community, warranting close attention to increased infection control measures and stewardship of the β-lactam-containing drugs in an effort to control selection of even more deleterious pathogens.

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Section: Carbapenemase-producing Bacteriamentioning

confidence: 99%

Epidemiology of β-Lactamase-Producing Pathogens

Bush

Bradford²

2020

Clin Microbiol Rev

572

440

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“…SHV ESBL variants are still identified, but few new TEM-related enzymes are now seen. Only recently have tazobactam-resistant CTX-M ␤-lactamases been identified, unusual enzymes that are still inhibited by clavulanic acid (128,129). The family of GES enzymes was initially believed to represent another set of ESBLs, but some GES variants with single point mutations have acquired the ability to hydrolyze carbapenems (130,131).…”

Section: ␤-Lactamases In Gram-negative Bacteriamentioning

confidence: 99%

Past and Present Perspectives on β-Lactamases

Bush

2018

Antimicrob Agents Chemother

658

498

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β-Lactamases, the major resistance determinant for β-lactam antibiotics in Gram-negative bacteria, are ancient enzymes whose origins can be traced back millions of years ago. These well-studied enzymes, currently numbering almost 2,800 unique proteins, initially emerged from environmental sources, most likely to protect a producing bacterium from attack by naturally occurring β-lactams. Their ancestors were presumably penicillin-binding proteins that share sequence homology with β-lactamases possessing an active-site serine. Metallo-β-lactamases also exist, with one or two catalytically functional zinc ions. Although penicillinases in Gram-positive bacteria were reported shortly after penicillin was introduced clinically, transmissible β-lactamases that could hydrolyze recently approved cephalosporins, monobactams, and carbapenems later became important in Gram-negative pathogens. Nomenclature is based on one of two major systems. Originally, functional classifications were used, based on substrate and inhibitor profiles. A later scheme classifies β-lactamases according to amino acid sequences, resulting in class A, B, C, and D enzymes. A more recent nomenclature combines the molecular and biochemical classifications into 17 functional groups that describe most β-lactamases. Some of the most problematic enzymes in the clinical community include extended-spectrum β-lactamases (ESBLs) and the serine and metallo-carbapenemases, all of which are at least partially addressed with new β-lactamase inhibitor combinations. New enzyme variants continue to be described, partly because of the ease of obtaining sequence data from whole-genome sequencing studies. Often, these new enzymes are devoid of any phenotypic descriptions, making it more difficult for clinicians and antibiotic researchers to address new challenges that may be posed by unusual β-lactamases.

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“…The CTX-M-190 is the first inhibitor-resistant CTX-M variant detected in clinical E. coli isolates that, together with CTX-M-199, retained hydrolytic activity on expanded-spectrum cephalosporins [ 57 , 58 ]. These variants arose due to the Ser-to-Thr amino acid substitution at positions 130 of CTX-M-55 and CTX-M-64, respectively.…”

Section: β-Lactam Molecular Resistance In Enterobacteriamentioning

confidence: 99%

Molecular Mechanisms, Epidemiology, and Clinical Importance of β-Lactam Resistance in Enterobacteriaceae

Angelis

Giacomo

Posteraro

et al. 2020

IJMS

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Despite being members of gut microbiota, Enterobacteriaceae are associated with many severe infections such as bloodstream infections. The β-lactam drugs have been the cornerstone of antibiotic therapy for such infections. However, the overuse of these antibiotics has contributed to select β-lactam-resistant Enterobacteriaceae isolates, so that β-lactam resistance is nowadays a major concern worldwide. The production of enzymes that inactivate β-lactams, mainly extended-spectrum β-lactamases and carbapenemases, can confer multidrug resistance patterns that seriously compromise therapeutic options. Further, β-lactam resistance may result in increases in the drug toxicity, mortality, and healthcare costs associated with Enterobacteriaceae infections. Here, we summarize the updated evidence about the molecular mechanisms and epidemiology of β-lactamase-mediated β-lactam resistance in Enterobacteriaceae, and their potential impact on clinical outcomes of β-lactam-resistant Enterobacteriaceae infections.

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Genetic and Functional Characterization of bla _CTX-M-199 , a Novel Tazobactam and Sulbactam Resistance-Encoding Gene Located in a Conjugative mcr-1 -Bearing IncI2 Plasmid

Abstract: We report the genetic and functional characterization of a novel CTX-M-199 ␤-lactamase, which was encoded by a bla CTX-M-64 variant gene found in a conjugative mcr-1-bearing IncI2 plasmid and exhibited resistance to ␤-lactamase inhibitors, tazobactam, and sulbactam.

Cited by 19 publications

References 13 publications

Epidemiology of β-Lactamase-Producing Pathogens

Epidemiology of β-Lactamase-Producing Pathogens

Past and Present Perspectives on β-Lactamases

Molecular Mechanisms, Epidemiology, and Clinical Importance of β-Lactam Resistance in Enterobacteriaceae

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Genetic and Functional Characterization of bla CTX-M-199 , a Novel Tazobactam and Sulbactam Resistance-Encoding Gene Located in a Conjugative mcr-1 -Bearing IncI2 Plasmid

Abstract: We report the genetic and functional characterization of a novel CTX-M-199 ␤-lactamase, which was encoded by a bla CTX-M-64 variant gene found in a conjugative mcr-1-bearing IncI2 plasmid and exhibited resistance to ␤-lactamase inhibitors, tazobactam, and sulbactam.

Cited by 19 publications

References 13 publications

Epidemiology of β-Lactamase-Producing Pathogens

Epidemiology of β-Lactamase-Producing Pathogens

Past and Present Perspectives on β-Lactamases

Molecular Mechanisms, Epidemiology, and Clinical Importance of β-Lactam Resistance in Enterobacteriaceae

Contact Info

Product

Resources

About

Genetic and Functional Characterization of bla _CTX-M-199 , a Novel Tazobactam and Sulbactam Resistance-Encoding Gene Located in a Conjugative mcr-1 -Bearing IncI2 Plasmid