Research Article Open Access

Complexity, Heterogeneity and Mutational Analysis of Antibiotic Inactivating Acetyl Transferases in MDR Conjugative Plasmids Conferring Multi-Resistance

Abstract

Drug acetylating transferases (aac) are enzymes that inactivate aminoglycoside antibiotics by acetylating its O- and N- atom in the drug. aac genes were detected in bacterial plasmids and integrons of many pathogenic bacteria rendering drug resistance. The unique CAT enzyme was discovered early that could acetylate chloramphenicol at 1’ and 3’ –OH group and largely used as reporter gene in expression vectors. Aminoglycoside 6’-N-acetylating enzymes were mainly classified as acc6’-Ia to aac6’-If and genes were designated as aacA1 to aacA8 but aacA16 or aacA41 types isomers were also sequenced. The isomers aacA3, aacA4 and aacA8 are very identical contrary to other aacA1 isomers. Aminoglycosides 3’-acetylating enzymes were designated as aac3’-Ia to aac3’-Xa and genes were designated as aacC1 to aacC10. Sequence analysis suggested that aac2’, aac4’ and bifunctional enzymes (aac6’-aph2’’) were different class of acetylating enzymes. But aac6’-1b-cr protein that was involved in ciprofloxacin resistance resembled to aac6’-1b with point mutations. Interestingly, cat gene has no similarity to aacA1 or aacC1 genes and so far was ignored as being non-clinical origin. But now catB3 gene was reported in many MDR plasmids of pathogens like Shigella flexneri (pR100), Yersinia pestis (pIP1202), Escherichia coli (pNR1), Pseudomonas aeruginosa (pOZ176), Klebsiella pneumoniae (pNDM-MAR) and Salmonella enterica (pHXY0908). Such plasmids were also frequently associated with acc3’ and aac6’ enzymes including diverged ß-lactamase genes (blaTEM, blaNDM, blaCTX-M etc) and drugs efflux genes (acrAB, mexAB/ CD/XY, tetA/S) as well as AG adenyl transferases (aad) and AG phospho transferases (aph) genes. Surely, appearance of cat, amp, tet genes in conjugative plasmids of superbugs is frightening as those genes are randomly used in expression vectors for RDT work. Diversities among drug acetylating enzymes were found very high suggesting multiple mechanisms of their origin.

Asit Kumar Chakraborty, Mitali Maity, Sabuj Patra, Suchismita Mukherjee and Tanmoy Mondal

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