Theβ-lactams—a large class of diverse compounds—due to their excellent safety profile and broad antimicrobial spectrum are considered to be the most widely used therapeutic class of antibacterials prescribed in human and veterinary clinical practices. This, unfortunately, has also given rise to a continuous increased resistance globally in health care settings as well as in the community due to their permanent selective force driving diversification of the resistance mechanism. Resistance againstβ-lactams is increasing rapidly as novelβ-lactamases, enzymes that degradeβ-lactams, are being discovered each day such as recent emergence of extended spectrumβ-lactamases (ESBL) that have the ability to inactivate most of the cephalosporins. The complexity and diversity of ESBL are increasing so rapidly that more than 170 variants have thus far been described for only a single genotype, theblaCTX-M-encoding ESBL. This review is to organize all the current updated literature describing genomic features, organization, and mechanism of resistance and mode of dissemination of all known ESBLs.

Prevalence of pathogenic multi-drug resistant (MDR) extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is rapidly increasing, becoming a global concern. In a veterinary context, ESBL-producing E. coli are mostly reported in poultry and pigs. Here, we report on the prevalence and characterize ESBL-producing E. coli isolated from diverse dairy farms in China. Overall, 36 (23.53%) out of 153 E. coli isolates from mastitic milk samples (n=1252) were confirmed as ESBL-producers by double-disc synergy testing and PCR. Nucleotide analysis of PCR amplicons revealed that blaCTX-M was the predominant ESBL gene detected in 28 (77.78%) isolates, with blaCTX-M-15 being the major (78.57%) allele encoding for ESBLs. Also, 22 (55.56%) and 6 (16.67%) of the ESBL isolates were carrying blaTEM and blaSHV genes, respectively, in singlet or in combination. The majority of these isolates belonged to phylo-group A (69.44%) and D (16.67%). Strikingly, all these isolates were found MDR reflecting high resistance (58-100%) to cephalosporins, including the fourth generation cefepime and non β-lactams. Additionally, class 1 integrons (intI1) were found in 30 (83.33%) isolates. Analysis of the integron 1 variable region encoding gene cassette indicated that they were carrying up to five different gene cassettes conferring resistance to various drugs with a predominant combination of dfrA17-aadA5 genes in tandem. However, no ESBL encoding genes were found in the cassettes. Interestingly, 22 (66.11%) of the ESBL isolates were also carrying insertion sequence common region 1 (ISCR1) which was found associated with most of the ESBL genes. Altogether, the current report on the high prevalence of ESBL-positive E. coli, particularly CTX-M-15, carrying integron 1 and ISCR1 elements are likely indicative of their rapid and wider dissemination, posing threats to veterinary and public health. To the best of our knowledge, this is the first comprehensive study to report on the alarming high occurrence of ESBL-producing E. coli from mastitic cows in China.

Characteristics and genetic diversity of multi-drug resistant extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli isolated from bovine mastitis Characteristics and genetic diversity of multi-drug resistant extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli isolated from bovine mastitis