IND-6, a Highly Divergent IND-Type Metallo-β-Lactamase fromChryseobacterium indologenesStrain 597 Isolated in Burkina Faso

Abstract

The genus Chryseobacterium and other genera belonging to the family Flavobacteriaceae include organisms that can behave as human pathogens and are known to cause different kinds of infections. Several species of Flavobacteriaceae, including Chryseobacterium indologenes, are naturally resistant to ␤-lactam antibiotics (including carbapenems), due to the production of a resident metallo-␤-lactamase. Although C. indologenes presently constitutes a limited clinical threat, the incidence of infections caused by this organism is increasing in some settings, where isolates that exhibit multidrug resistance phenotypes (including resistance to aminoglycosides and quinolones) have been detected. Here, we report the identification and characterization of a new IND-type variant from a C. indologenes isolate from Burkina Faso that is resistant to ␤-lactams and aminoglycosides Metallo-␤-lactamases (MBLs) belong to Ambler's class B, and their activity requires at least one zinc ion in the active site. These enzymes are particularly worrisome resistance determinants due to their ability to hydrolyze most ␤-lactam compounds, including carbapenems, while they are not susceptible to conventional ␤-lactamase inhibitors (e.g., clavulanic acid, sulbactam, and tazobactam) (25). Besides the acquired MBL genes which currently disseminate in major human pathogens (e.g., Pseudomonas aeruginosa) by means of mobile genetic elements (plasmids, integrons, or ISCR elements), most MBL genes identified thus far have been found in the chromosomes of various bacterial species, including nonpathogenic organisms (such as Caulobacter crescentus), plant pathogens (Erwinia carotovora), and occasional human pathogens such as Stenotrophomonas maltophilia, Aeromonas spp., and members of the family Flavobacteriaceae (25, 32). The latter family includes several species in which the production of a resident MBL has been detected. Although their overall clinical impact is lower than that of Enterobacteriaceae, Pseudomonas, or Acinetobacter species, Flavobacteriaceae may cause various clinical syndromes that are not always straightforward to treat, due mainly to their intrinsic resistance to several antimicrobial agents (29). Eight different sublineages of resident enzymes in members of the family Flavobacteriaceae have been identified thus far (4-7, 18, 20, 26), and most of them (BlaB from Elizabethkingia meningoseptica, IND from Chryseobacterium indologenes, JOHN from Flavobacterium johnsoniae, CGB from Chryseobacterium gleum, EBR from Empedobacter brevis, TUS from Myroides odoratus, and MUS from Myroides odoratimimus) belong to subclass B1, although the GOB enzymes (from E. meningoseptica) belong to subclass B3.The most common flavobacterium from clinical specimens is C. indologenes, which is associated with different types of infections, such as intra-abdominal and urinary tract infections, catheter-related bacteremia, cellulitis, sepsis, and pneumonia, likely promoted by the bacterium's ability to form biofilm and to produce proteases (1,3,15,16,21,23,24...

Characterization of CIA-1, an Ambler Class A Extended-Spectrum β-Lactamase from Chryseobacterium indologenes

“…The mature peptide has a theoretical pI of 9.0, which corresponded to the pI of CIA-1 by isoelectric focusing (data not shown). It is probably the same ␤-lactamase band observed by Zeba et al (19). The susceptibility of C. indologenes ATCC 29897 to ␤-lactams was similar to that reported for C. indologenes (13).…”

“…CGA-1 and CME exhibit broad-spectrum profiles and are chromosomally encoded. Zeba et al reported a single ␤-lactamase band at pI 9.0 in addition to IND from C. indologenes, using isoelectric focusing, and the band at pI 9.0 probably included an active site serine enzyme (19). However, no class A ␤-lactamases have been identified from C. indologenes.…”

Chryseobacterium indologenes: An Emerging Hospital Infection

“…C. indologenes is also intrinsically resistant to carbapenems and cephalosporins due to its production of molecular class A β-lactamase [10] and Class B carbapenemhydrolyzing β-lactamase (IND1-IND7). [13,14] In addition, the results of susceptibility testing vary when different methods are used. However, in vitro susceptibilities determined by the disk diffusion method showed poor correlation compared with the broth microdilution method, which is the preferred methodology.…”

Chryseobacterium indologenes: an emerging infection in the USA

“…Its ability to produce biofilm on foreign materials and produce proteases, can cause several forms of infections and is responsible for its virulent character 31. One study mentioned the production of a metallo-β-lactamase, which allows the bacteria to hydrolyse the β lactam part of some drugs 32. It was sensitive to a limited number of antibiotics that include newer quinolones, in particular, garenoxacin, gatifloxacin and levofloxacin, rifampin, trimethoprim-sulfamethoxazole and piperacillin-tazobactam 22.…”