A link between zinc uptake, bile salts, and a capsule required for virulence of a mastitis-associated extraintestinal pathogenicEscherichia colistrain

Abstract

21Extraintestinal pathogenic Escherichia coli (ExPEC) are major causes of urinary and 22 bloodstream infections. ExPEC reservoirs are not completely understood. Some mastitis-23 associated E. coli (MAEC) strains carry genes associated with ExPEC virulence, including metal 24 scavenging, immune avoidance, and host attachment functions. In this study, we investigated the 25 role of the high-affinity zinc uptake (znuABC) system in the MAEC strain M12. Elimination of 26 znuABC moderately decreased fitness during mouse mammary gland infections. The znuABC 27 mutant strain exhibited an unexpected growth delay in the presence of bile salts, which was 28 alleviated by the addition of excess zinc. We isolated znuABC mutant suppressor mutants with 29 improved growth of in bile salts, several of which no longer produced the K96 capsule made by 30 strain M12. Addition of bile salts also reduced capsule production by strain M12 and ExPEC 31 strain CP9, suggesting that capsule synthesis may be detrimental when bile salts are present. To 32 better understand the role of the capsule, we compared the virulence of mastitis strain M12 with 33 its unencapsulated kpsCS mutant in two models of ExPEC disease. The wild type strain 34 successfully colonized mouse bladders and kidneys and was highly virulent in intraperitoneal 35 infections. Conversely, the kpsCS mutant was unable to colonize kidneys and was unable to 36 cause sepsis. These results demonstrate that some MAEC may be capable of causing human 37 ExPEC illness. Virulence of strain M12 in these infections is dependent on its capsule. However, 38 capsule may interfere with zinc homeostasis in the presence of bile salts while in the digestive 39 tract. 40 41 42 43

Poly-gamma-glutamic acid secretion protects Bacillus subtilis from zinc and copper intoxication

“…Additionally, excess zinc decreases Streptococcus pyogenes hyaluronic acid capsule production by inhibiting phosphoglucomutase, a key enzyme in central carbon metabolism (11). Recent studies on Escherichia coli virulence suggest that the presence of capsule may exacerbate bile salt mediated zinc starvation (12).…”