Influence of iron deprivation on virulence traits of mycobacteria

Abstract

Novel strategies to combat the ever increasing burden of drug resistance in Mycobacterium tuberculosis (MTB) causing tuberculosis (TB) remains a global concern. The ability of MTB to sense and adapt to restricted iron conditions in the hostile environment is essential for their survival and confers the basis of their success as dreadful pathogen. The striking and clinically relevant virulence trait of MTB is its ability to form biofilms and adhere to the host cells. The present study elucidated the effect of iron deprivation on biofilm formation and cell adherence of Mycobacterium smegmatis, a non-pathogenic surrogate of MTB. Firstly, we showed that iron deprivation leads to enhanced cell sedimentation rate and altered colony morphology depicting alterations in cell surface envelope properties. We explored that biofilm formation and cell adherence to polystyrene surface as well as human oral epithelial cells were considerably reduced under iron deprivation both in presence of 2,2 BP (iron chelator) and siderophore mutant Δ011-14 strain. We further investigated that the potency of three first line anti-TB drugs (Isoniazid, Ethambutol, Rifampicin) to inhibit both biofilm formation and cell adhesion were enhanced under iron deprivation in contrast to the drugs when tested alone. Taken together, by virtue of the indispensability of iron for functional virulence traits in mycobacteria, iron deprivation strategies could be further exploited against this notorious human pathogen to explore novel drug targets.

Elucidating the Mechanism of Vanillin Induced Mycobacterial Membrane Disruption: Implications of Lipid Alteration

“…Interestingly, in presence of Van, we could observe colonies which have undefined and rough borders (Figure 5a). To further substantiate our findings, cell sedimentation rate in presence of Van was monitored that could be attributed to changes in cell surface hydrophobicity [18,34]. We estimated that cell sedimentation rate was enhanced in presence of Van possibly due to the fact that cell envelope of mycobacteria have unique lipid classes which are known to govern pathogenicity and that Van could have led to certain alterations in those lipid classes (Figure 5b).…”

“…Mycobacterium posses hydrophobic lipid which gives the smooth surface that contribute virulence factor of Mycobacterium. From the previous studies it is known that cell surface hydrophobicity affect the colony morphology of Mycobacterium [18]. Alteration in membrane lipid may therefore interfere with colony morphology of Mycobacterium [32].…”

“…Colony morphology was determined as by a protocol as described elsewhere [18]. Briefly, cells were plated in the presence and absence of Van on Middlebrook agar plates supplemented with 10% OADC and incubated at 37°C for 2 to 4 days.…”

“…Cell sedimentation assay was performed as described elsewhere [18]. Cultures at OD 600 ~ 1.0-1.4 of the control and cells treated with sub-inhibitory concentration 15µg/ml in Middlebrook media supplemented with ADC were adjusted in triplicate to OD 590 ~ 1.0 and kept unshaken at 37°C.…”

Antimycobacterial Effect and Mechanisms of Monoterpenoid, Perillyl Alcohol

“…Colony morphology and sliding motility were determined as described elsewhere [14]. Briefly, cells were plated on MB7H10 agar plates supplemented with 10% OADC (BD Difco) and incubated at 37°C for 2 to 4 days.…”