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.

Contact Effect of a Methylobacterium sp. Extract on Biofilm of a Mycobacterium chimaera Strain Isolated from a 3T Heater-Cooler System

“…Though it is known that most mycobacteria resist destruction for long periods in the dry state in the absence of sunlight [57] and that non-homologous end-joining pathway is involved in this phenomenon at least in Mycobacterium smegmatis [58], this does not mean that mycobacterial biofilms do not reduce their bacterial concentration over time at room temperature. This viability reduction may be result of an autolytic mechanism of certain mycobacteria from biofilm which would immolate themselves for the sake of their adjacent congeners [40,59], at the same time that they would weaken structurally their biofilm and make it more permeable [59,60] to the Methylobacterium extract and its antimycobacterial effect. These results might support the use of this extract with antibiotics or antiseptics after desiccation period of the equipment, since the Methylobacterium extract used in combination with clarithromycin was able to inhibit the M. abcessus biofilm development over time by reducing the biofilm covered area and its thickness compared to the clarithromycin control [61].…”

Pulmonary non-tuberculous mycobacterial infections: current state and future management

“…Thus, the risk of PNTM could be potentially associated with the percentage of surface water, temperature, humidity, rain precipitation and potential of evaporation and transpiration, whereby aerolization, favoured by the mycobacterial hydrophobicity and inhalation of water droplets contribute to PNTM [230]. The hydrophobicity promotes bacterial adherence at surfaces and pellicle biofilm formation at the liquid-air interface [224].…”

Mycobacterium tuberculosis PE31 (Rv3477) Attenuates Host Cell Apoptosis and Promotes Recombinant M. smegmatis Intracellular Survival via Up-regulating GTPase Guanylate Binding Protein-1

“…The bacterial cell wall is not only providing protection to the bacteria but also crucial for its pathogenesis and virulence (Abrahams and Besra, 2018). Modification in the mycobacterial cell wall components such as glycopeptidolipids usually accompanies with alteration in colony morphology and biofilm formation (Chakraborty and Kumar, 2019). Many members of PE family protein are localized and associated with the mycobacterial cell wall (Sultana et al, 2016) and secreted into the extracellular environment to interact with neighboring cells (Beatty and Russell, 2000;Beatty et al, 2001;Yu et al, 2019).…”