Intraspecies and Temperature-Dependent Variations in Susceptibility of Yersinia pestis to the Bactericidal Action of Serum and to Polymyxin B

Abstract

Lipopolysaccharide (LPS) structure impacts the bactericidal action of cationic peptides, such as polymyxin B (PMB), and sensitivity to killing by normal human serum (NHS). Cultivation of different subspecies strains of Yersinia pestis isolated from unrelated geographic origins at various temperatures (mammals, 37°C; fleas, 25°C; or winter hibernation, 6°C) affects LPS composition and structure. We tested the susceptibilities of various strains of Y. pestis grown at these different temperatures to PMB and serum bactericidal killing. Both properties varied significantly in response to temperature changes. In Y. pestis subsp. pestis (the main subspecies causing human plague), high levels of resistance to PMB and NHS were detected at 25°C. However, at the same temperature, Y. pestis subsp. caucasica was highly sensitive to PMB. At both of the extreme temperatures, all strains were highly susceptible to PMB. At 25°C and 37°C, Y. pestis subsp. caucasica strain 1146 was highly susceptible to the bactericidal activity of 80% NHS. All Y. pestis strains studied were able to grow in heatinactivated human serum or in 80% normal mouse serum. At 6°C, all strains were highly sensitive to NHS. Variations in the PMB resistance of different bacterial cultures related to both the content of cationic components (4-amino-4-deoxyarabinose in lipid A and glycine in the core) and a proper combination of terminal monosaccharides in the LPS. The NHS resistance correlated with an elevated content of N-acetylglucosamine in the LPS. Structural variation in the LPS of Y. pestis correlates with the organism's ability to resist innate immunity in both fleas and mammals.

Role of immune response in Yersinia pestis infection

“…In contrast to enteropathogenic yersiniae, which are resistant to complement when grown at 37°C but not when grown at 26°C, Y. pestis is resistant to complement at both temperatures [23]. In enteropathogenic yersiniae, this function is mediated by YadA, which is not expressed in Y. pestis, and LPS, which seems to play a major role in the resistance to serum-mediated lysis [24]. However, the Y. pestis strains deficient in the expression of Ail are extremely sensitive to complement and the study performed by the Plano group suggests that Ail might be an essential complement resistance factor due to its requirement for full protection of Y. pestis from in vitro complement-mediated lysis [25].…”

“…In addition, to survive and grow in blood for transmission between its flea vector and the mammalian host, Y. pestis has developed resistance to complement-mediated lysis [23,24,25]. In contrast to enteropathogenic yersiniae, which are resistant to complement when grown at 37°C but not when grown at 26°C, Y. pestis is resistant to complement at both temperatures [23].…”

Molecular Basis of Yersinia enterocolitica Temperature-Dependent Resistance to Antimicrobial Peptides

“…At 21°C the lipid A is mainly hexa-acylated (39,64). The substitution of the lipid A with aminoarabinose is also temperature regulated, being higher at 21°C than at 37°C (1,64). In other bacteria, the lipid A modification with aminoarabinose is linked to the resistance to polymyxin B, commonly used to demonstrate AP resistance in laboratory settings.…”

Characterization of the Six Glycosyltransferases Involved in the Biosynthesis of Yersinia enterocolitica Serotype O:3 Lipopolysaccharide Outer Core

“…The resistance of the strains to polymyxin B was temperature-dependent, and the minimal inhibitory concentrations were higher at room temperature than at 37°C (Table 5). This is a general feature of Yersiniae (47)(48)(49), and the molecular bases of it are still poorly understood. In strains expressing OPS, all the mutants expressing truncated OC were more susceptible to polymyxin B than the wild type.…”