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The extracellular matrix of mycobacterial biofilms: could we shorten the treatment of mycobacterial infections?

ABSTRACT: A number of non-tuberculous mycobacterium species are opportunistic pathogens and ubiquitously form biofilms. These infections are often recalcitrant to treatment and require therapy with multiple drugs for long duration. The biofilm resident bacteria also display phenotypic drug tolerance and thus it has been hypothesized that the drug unresponsiveness in vivo could be due to formation of biofilms inside the host. We have discussed the biofilms of several pathogenic non-tuberculous mycobacterium (NTM) species in context to the in vivo pathologies. Besides pathogenic NTMs, Mycobacterium smegmatis is often used as a model organism for understanding mycobacterial physiology and has been studied extensively for understanding the mycobacterial biofilms. A number of components of the mycobacterial cell wall such as glycopeptidolipids, short chain mycolic acids, monomeromycolyl diacylglycerol, etc. have been shown to play an important role in formation of pellicle biofilms. It shall be noted that these components impart a hydrophobic character to the mycobacterial cell surface that facilitates cell to cell interaction. However, these components are not necessarily the constituents of the extracellular matrix of mycobacterial biofilms. In the end, we have described the biofilms of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. Three models of Mtb biofilm formation have been proposed to study the factors regulating biofilm formation, the physiology of the resident bacteria, and the nature of the biomaterial that holds these bacterial masses together. These models include pellicle biofilms formed at the liquid-air interface of cultures, leukocyte lysate-induced biofilms, and thiol reductive stressinduced biofilms. All the three models offer their own advantages in the study of Mtb biofilms. Interestingly, lipids (mainly keto-mycolic acids) are proposed to be the primary component of extracellular polymeric substance (EPS) in the pellicle biofilm, whereas the leukocyte lysate-induced and thiol reductive stress-induced biofilms possess polysaccharides as the primary component of EPS. Both models also contain extracellular DNA in the EPS. Interestingly, thiol reductive stressinduced Mtb biofilms are held together by cellulose and yet unidentified structural proteins. We believe that a better understanding of the EPS of Mtb biofilms and the physiology of the resident bacteria will facilitate the development of shorter regimen for TB treatment.

SUBMITTER: Chakraborty P

PROVIDER: S-EPMC6364259 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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The extracellular matrix of mycobacterial biofilms: could we shorten the treatment of mycobacterial infections?

Chakraborty Poushali P Kumar Ashwani A

Microbial cell (Graz, Austria) 20190118 2

A number of non-tuberculous mycobacterium species are opportunistic pathogens and ubiquitously form biofilms. These infections are often recalcitrant to treatment and require therapy with multiple drugs for long duration. The biofilm resident bacteria also display phenotypic drug tolerance and thus it has been hypothesized that the drug unresponsiveness <i>in vivo</i> could be due to formation of biofilms inside the host. We have discussed the biofilms of several pathogenic non-tuberculous mycob ...[more]

PMID: 30740456

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Project description:UnlabelledBacterial biofilms are ubiquitous in nature, and their resilience is derived in part from a complex extracellular matrix that can be tailored to meet environmental demands. Although common developmental stages leading to biofilm formation have been described, how the extracellular components are organized to allow three-dimensional biofilm development is not well understood. Here we show that uropathogenic Escherichia coli (UPEC) strains produce a biofilm with a highly ordered and complex extracellular matrix (ECM). We used electron microscopy (EM) techniques to image floating biofilms (pellicles) formed by UPEC. EM revealed intricately constructed substructures within the ECM that encase individual, spatially segregated bacteria with a distinctive morphology. Mutational and biochemical analyses of these biofilms confirmed curli as a major matrix component and revealed important roles for cellulose, flagella, and type 1 pili in pellicle integrity and ECM infrastructure. Collectively, the findings of this study elucidated that UPEC pellicles have a highly organized ultrastructure that varies spatially across the multicellular community.ImportanceBacteria can form biofilms in diverse niches, including abiotic surfaces, living cells, and at the air-liquid interface of liquid media. Encasing these cellular communities is a self-produced extracellular matrix (ECM) that can be composed of proteins, polysaccharides, and nucleic acids. The ECM protects biofilm bacteria from environmental insults and also makes the dissolution of biofilms very challenging. As a result, formation of biofilms within humans (during infection) or on industrial material (such as water pipes) has detrimental and costly effects. In order to combat bacterial biofilms, a better understanding of components required for biofilm formation and the ECM is required. This study defined the ECM composition and architecture of floating pellicle biofilms formed by Escherichia coli.

Project description:Extracellular DNA (eDNA) is an integral biofilm matrix component of numerous pathogens, including nontuberculous mycobacteria (NTM). Cell lysis is the source of eDNA in certain bacteria, but the source of eDNA remains unidentified for NTM, as well as for other eDNA-containing bacterial species. In this study, conditions affecting eDNA export were examined, and genes involved with the eDNA export mechanism were identified. After a method for monitoring eDNA in real time in undisturbed biofilms was established, different conditions affecting eDNA were investigated. Bicarbonate positively influenced eDNA export in a pH-independent manner in Mycobacterium avium, M. abscessus, and M. chelonae The surface-exposed proteome of M. avium in eDNA-containing biofilms revealed abundant carbonic anhydrases. Chemical inhibition of carbonic anhydrases with ethoxzolamide significantly reduced eDNA export. An unbiased transposon mutant library screen for eDNA export in M. avium identified many severely eDNA-attenuated mutants, including one not expressing a unique FtsK/SpoIIIE-like DNA-transporting pore, two with inactivation of carbonic anhydrases, and nine with inactivation of genes belonging to a unique genomic region, as well as numerous mutants involved in metabolism and energy production. Complementation of nine mutants that included the FtsK/SpoIIIE and carbonic anhydrase significantly restored eDNA export. Interestingly, several attenuated eDNA mutants have mutations in genes encoding proteins that were found with the surface proteomics, and many more mutations are localized in operons potentially encoding surface proteins. Collectively, our data strengthen the evidence of eDNA export being an active mechanism that is activated by the bacterium responding to bicarbonate. IMPORTANCE:Many bacteria contain extracellular DNA (eDNA) in their biofilm matrix, as it has various biological and physical functions. We recently reported that nontuberculous mycobacteria (NTM) can contain significant quantities of eDNA in their biofilms. In some bacteria, eDNA is derived from dead cells, but that does not appear to be the case for all eDNA-containing organisms, including NTM. In this study, we found that eDNA export in NTM is conditionally dependent on the molecules to which the bacteria are exposed and that bicarbonate positively influences eDNA export. We also identified genes and proteins important for eDNA export, which begins to piece together a description of a mechanism for eDNA. Better understanding of eDNA export can give new targets for the development of antivirulence drugs, which are attractive because resistance to classical antibiotics is currently a significant problem.

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The extracellular matrix of mycobacterial biofilms: could we shorten the treatment of mycobacterial infections?

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The extracellular matrix of mycobacterial biofilms: could we shorten the treatment of mycobacterial infections?

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