Variant O89 O-Antigen of Is Associated With Group 1 Capsule Loci and Multidrug Resistance.
Susan Harris, Marta J Piotrowska, Robert J Goldstone, Ruby Qi, Geoffrey Foster, Ulrich Dobrindt, Jean-Yves Madec, Charlotte Valat, Francesco V Rao, David G E Smith
Author Information
Susan Harris: Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh, United Kingdom.
Marta J Piotrowska: Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh, United Kingdom.
Robert J Goldstone: The Francis Crick Institute, London, United Kingdom.
Ruby Qi: Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh, United Kingdom.
Bacterial surface polysaccharides play significant roles in fitness and virulence. In Gram-negative bacteria such as , major surface polysaccharides are lipopolysaccharide (LPS) and capsule, representing O- and K-antigens, respectively. There are multiple combinations of O:K types, many of which are well-characterized and can be related to ecotype or pathotype. In this investigation, we have identified a novel O:K permutation resulting through a process of major genome reorganization in a clade of . A multidrug-resistant, extended-spectrum β-lactamase (ESBL)-producing strain - 26561 - represented a prototype of strains combining a locus variant of O89 and group 1 capsular polysaccharide. Specifically, the variant O89 locus in this strain was truncated at , flanked by insertion sequences and located between and and we apply the term O89m for this variant. The prototype lacked colanic acid and O-antigen loci between and with this tandem polysaccharide locus being replaced with a group 1 capsule (G1C) which, rather than being a recognized capsule type, this locus matched to K10 capsule type. A genomic survey identified more than 200 strains which possessed the O89m locus variant with one of a variety of G1C types. Isolates from our collection with the combination of O89m and G1C all displayed a mucoid phenotype and 26561 was unusual in exhibiting a mucoviscous phenotype more recognized as a characteristic among strains. Despite the locus truncation and novel location, all O89m:G1C strains examined showed a ladder pattern typifying smooth LPS and also showed high molecular weight, alcian blue-staining polysaccharide in cellular and/or extra-cellular fractions. Expression of both O-antigen and capsule biosynthesis loci were confirmed in prototype strain 26561 through quantitative proteome analysis. Further exploration of more than 200 strains possessing the O89m:G1C combination identified a very high prevalence of multidrug resistance (MDR) - 85% possessed resistance to three or more antibiotic classes and a high proportion (58%) of these carried ESBL and/or carbapenemase. The increasing isolation of O89m:G1C isolates from extra-intestinal infection sites suggests that these represents an emergent clade of invasive, MDR .
