Beta-lactamases

Beta-lactam antibiotics are a class of broad spectrum antibiotics, characterized by a ß-lactam ring in their structure.  The class of antibiotics include penicillins, cephalosporins, and the monobactam aztreonam.  Most ß-lactam antibiotics function by inhibiting bacterial cell wall biosynthesis. 

Antibiotic resistance to ß-lactam antibiotics is conferred in part by a set of enzymes that are able to rupture of the lactam amide bond of the ß-lactam antibiotic molecule, ultimately forming a serine ester-linked acyl derivative that no longer inhibits cell wall formation. 

Two types of proteins have been found to catalyze these reactions.  The first are the penicillin binding proteins (described on a second page), which have a low level of activity.  Higher activity levels are found in an extensive set of  ß-lactamase enzymes.   There are a variety of such enzymes found across the prokaryotic realm, and identification of such enzymes within Orientia depends upon searches for sequence similarity and ultimately homology of structure and function with genes found in other bacteria.

 

ß-LACTAMASE ENZYMES IN ORIENTIA

Examination of the genome sequences of isolates of O. tsutsugamushi and O. chuto have revealed the existence of two ß-lactamase related loci.  Both loci were found to be present in all of the 14 O. tsutsugamushi genomes examined and in the genome of O. chuto.  Both loci showed variation between isolates at both the nucleic and amino acid levels.   The loci, and the location within the genome of the Boryong isolate. 

metallo-beta-lactamase family protein: Boryong – 1325832..1327568

phnP – “Metal-dependent hydrolases of the beta-lactamase superfamily I”
Boryong –  1847828..1848577