Bile Salts Regulate Zinc Uptake and Capsule Synthesis in a Mastitis-Associated Extraintestinal Pathogenic Escherichia coli Strain

Abstract

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

Gut microbiota-mediated secondary bile acid alleviates Staphylococcus aureus-induced mastitis through the TGR5-cAMP-PKA-NF-κB/NLRP3 pathways in mice

“…Interestingly, Thomas et al found a dynamic change in BA concentrations in milk after intramammary challenge with Streptococcus uberis 43 , implying the potential role of BAs in pathogen-induced mastitis. In addition, bile salts have been reported to regulate zinc uptake and capsule synthesis in a mastitis-associated pathogenic E. coli 44 , suggesting that different bile acids may have different effects on the host or pathogens.…”

Genes associated with fitness and disease severity in the pan-genome of mastitis-associatedEscherichia coli

“…We did find several instances of MAEC strains possessing genes with demonstrated roles in ExPEC virulence (Figure 2). Although these virulence factors were not associated with CM severity generally, it does not rule out the possibility that they contribute to the virulence of individual strains in MGs, as we have previously demonstrated for the capsule and zinc uptake gene clusters of strain M12 (21,30). Furthermore, additional factors continue to be recognized that contribute to ExPEC infections, and these may also be selected by the dairy environment and enriched in MAEC strains.…”

“…In addition to host factors, bacterial factors may also influence CM severity (17,28,29). Some MAEC strains carry virulence factors often found in human or avian extraintestinal pathogenic E. coli (ExPEC) such as toxins, siderophores, capsules and adhesins (30). For the most part, the influence of these virulence factors during intramammary infections has not been determined.…”

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 ).…”