Vaccines Directed Against Microorganisms or Their Products Present During Biofilm Lifestyle: Can We Make a Translation as a Broad Biological Model to Tuberculosis?

Abstract

Tuberculosis (TB) remains as a global public health problem. In recent years, experimental evidence suggesting the relevance of in vitro pellicle (a type of biofilm formed at the air-liquid interface) production as a phenotype mimicking aspects found by Mycobacterium tuberculosis-complex bacteria during in vivo infection has started to accumulate. There are still opportunities for better diagnostic tools, therapeutic molecules as well as new vaccine candidates to assist in TB control programs worldwide and particularly in less developed nations. Regarding vaccines, despite the availability of a live, attenuated strain (Mycobacterium bovis BCG) since almost a century ago, its variable efficacy and lack of protection against pulmonary and latent disease has prompted basic and applied research leading to preclinical and clinical evaluation of up to 15 new candidates. In this work, I present examples of vaccines based on whole cells grown as biofilms, or specific proteins expressed under such condition, and the effect they have shown in relevant animal models or directly in the natural host. I also discuss why it might be worthwhile to explore these approaches, for constructing and developing new vaccine candidates for testing their efficacy against TB.

Complete nitrification: insights into the ecophysiology of comammox Nitrospira

“…The metabolic function of this type of hydrogenase in complete nitrifiers remains to be determined and might include (i) H 2 oxidation as alternative or additional electron source for energy conservation and/or CO 2 fixation, (ii) H 2 evolution for maintaining the redox balance during anaerobic degradation of simple organic matter (as suggested by Kits et al 2017 ), and (iii) H 2 S production for sulfur assimilation. Moreover, the identification of group 3b hydrogenases in canonical ammonia and nitrite oxidizer genomes, like the marine NOB Nitrococcus mobilis (Füssel et al 2017 ), Nitrospina marina (Lücker et al 2013 ), and several AOB including Nitrosococcus halophilus Nc4 (GenBank accession number ADE14678.1) and Nitrosomonas mobilis (Thandar et al 2016 ) emphasizes the need to characterize the physiological function(s) of this enzyme in nitrifying bacteria. N. moscoviensis is the only Nitrospira species known to have recruited a different type of hydrogenase.…”

The BCGΔBCG1419c Vaccine Candidate Reduces Lung Pathology, IL-6, TNF-α, and IL-10 During Chronic TB Infection

“…In order to explore the hypothesis that mycobacterial biofilms resemble aspects of chronic TB infection ( Flores-Valdez, 2016 ), we deleted the cyclic di-GMP phosphodiesterase-encoding gene BCG1419c , to create the BCGΔBCG1419c Pasteur-derivative strain ( Flores-Valdez et al, 2015 ). We previously showed that in immunocompromised nu/nu mice, BCGΔBCG1419c was as safe as parental BCG, and that in a mouse model of progressive infection with M. tuberculosis H37Rv, compared to BCG, vaccination with BCGΔBCG1419c increased the levels of CD4 + and CD8 + T lymphocytes, and reduced 1-log 10 bacterial burden in lungs after 24 weeks post-infection, with reduced pneumonia, indicating its potential as a preventive vaccine against chronic TB ( Pedroza-Roldán et al, 2016 ).…”

Transcriptional portrait of M. bovis BCG during biofilm production shows genes differentially expressed during intercellular aggregation and substrate attachment

“…Moreover, BCG2232 (Rv2216) and TB39.8 (BCG0050c, Rv0020c, FhaA) were affected specifically after substratum attachment (FC = 1, and − 0.74 Log 2 , respectively, Supplementary Tables 4 and 5). The fact that some biofilm-specific proteins that were recognized in vivo had their encoding genes differentially expressed during biofilm production in vitro by BCG further strengthen the notion of biofilms mimicking aspects found during TB pathogenesis 26 . Taken together, our results show that dosR and BCG0114 were expressed in a temporal order during mycobacterial biofilm formation to produce biofilm-specific changes, which most likely are triggered in response to varying oxygen levels within biofilms.…”

“…Evidence reported over the last decade associate the capacity of M. tuberculosis-complex bacteria with virulence in ex vivo or in vivo models 26 . Pang et al 14 found several genes that were required for biofilm production using a "formation/no formation" readout, while Yang et al 1 utilized a genetic approach to propose a temporal order for development of mycobacterial biofilms using M. smegmatis as model.…”