The Type of Growth Medium Affects the Presence of a Mycobacterial Capsule and Is Associated With Differences in Protective Efficacy of BCG Vaccination AgainstMycobacterium tuberculosis

Abstract

The presence of detergent in growth media and a capsule on BCG were associated with differences in the outcome of vaccination, implying that these are important variables in immunological studies.

Differential Cultivation of Francisella tularensis Induces Changes in the Immune Response to and Protective Efficacy of Whole Cell-Based Inactivated Vaccines

“…Recently, BCG vaccine exhibited differential protective efficacy based on the presence or absence of detergents in the growth medium. The latter was associated with differential expression of capsular polysaccharides, the presence of capsule specific Ab, splenic IL-17 and IFN-γ production, and multifunctional CD4+ T cell responses (31). We have also observed differential protective efficacy of BHI- and MHB-grown live Ft LVS vaccine, where BHI-grown Ft LVS exhibited better protection against lethal infection with Ft SchuS4 (32).…”

Interplay of human macrophages and Mycobacterium tuberculosis phenotypes

“…We were however unable to detect ESAT6 in infected macrophages by immunolabeling, although ESAT6 clearly was present on bacilli before contact with macrophages. Our study as well as findings from others warrant a re-evaluation of cultivation conditions for experimental studies, since the sole presence of a mycobacterial capsule elicited differential responses in macrophages and in a murine vaccination model, and cultivation without detergent profoundly altered the transcriptome of Mtb [356,359].…”

“…Another study looking into the transcriptional response of bovine alveolar macrophages after M. bovis infection obtained conclusions different from other studies with similar settings, partly attributed to the use of detergent-free cultivated bacilli, but unfortunately a direct comparison of the transcriptomics upon infection of Mtb cultivated with or without detergent was not performed here [358]. Looking into the immunological response after BCG-vaccination and Mtb-challenge of mice, encapsulated BCG triggered a more potent immune response as compared to non-encapsulated (detergent-cultivated) BCG, featuring polyfunctional T cells, higher IFNγ production and lower CFU burden [359]. In line with earlier studies in mice mentioned above [352,353], an antibody response against capsular polysaccharides was observed.…”

Esx Systems and the Mycobacterial Cell Envelope: What's the Connection?

“…Specifically, mycobacterial strains are grown in vitro in the presence of detergent, usually either Tween 80 or tyloxapol, to reduce bacterial clumping during growth. Growth in detergent promotes the release of the mycobacterial capsule into the growth medium (4,168). When mycobacteria are grown without detergent, to promote the retention of the capsule, several ESX-1 and ESX-5 substrates are localized to the capsule layer (4,165,169).…”

“…Coupled with evidence that ESX-1 substrates are present in the capsule and on the cell surface, discovered by our group and several others, direct translocation of ESX-1 substrates into the host macrophage may not occur. Rather, the presence of ESX-1 substrates on the cell surface may be sufficient for promoting phagosomal lysis (134,(166)(167)(168)(169)(170)(171)(172)(173)(174)(175)(176)(177)(178)(179)(180)(181)(182)(183)(184)(185). Alternatively, contact with membranes may induce ESX-1 secretion through an unknown signal transduction mechanism.…”