Biology subjects

Hussain, M. S.

Publications and source records attributed to Hussain, M. S..

4 recordsLinked to original sources

bioRxiv2021

ErpY-like lipoprotein of Leptospira outsmart host complement regulation by acquiring complement regulators, activating alternate pathway, and intervening membrane attack complex

The survival of pathogenic Leptospira in the host pivots on its proficiency to circumvent the immune response. These pathogens evade the complement system in serum by enticing and amassing the serum complement regulators onto their surface. ErpY-like lipoprotein, a surface-exposed protein of Leptospira spp., is conserved and exclusively present in the pathogenic spirochete. The recombinant form of this protein is comprehended to interact with multiple extracellular matrix (ECM) components and serum proteins like soluble complement regulators factor H (FH) and factor I (FI). Here, we document that the supplementation of recombinant ErpY-like protein (40 {micro}g/mL) in the host (humans) serum augments the viability of E. coli and saprophytic L. biflexa by more than 2-fold. Pure complement regulators FH and FI, when bound to rErpY-like protein, preserve their respective cofactor and protease activity mandated to cleave the complement component C3b. The supplementation of rErpY-like protein (40 {micro}g/mL) in serum ensued in [~]90 % reduction of membrane attack complex (C5b-9/MAC) deposition through alternate complement pathway (AP) activation. However, rErpY-like protein could moderately reduce ([~]16%) MAC deposition in serum through the classical pathway (CP). In addition, the rErpY-like protein solely activated the AP, suggesting its role in the rapid consumption and depletion of the complement components. Blocking the pathogenic L. interrogans surface with anti-rErpY resulted in an increase in MAC formation on the bacterial surface, indicating a specific role of the ErpY-like lipoprotein in complement-mediated immune evasion. This study underscores the role of the ErpY-like lipoprotein of Leptospira in complement evasion.

microbiology↗

bioRxiv2020

ADEP1 activated ClpP1P2 macromolecule of Leptospira, an ideal Achilles' heel to deregulate proteostasis and hamper the cell survival

The caseinolytic protease (ClpP) complex in Leptospira interrogans is unusual in its functional activation. The genus Leptospira has two ClpPs, ClpP1 and ClpP2, which transcribes independently, regardless it couples to form the active tetradecamer. Acyldepsipeptide (ADEP) antibiotic hampers the growth of numerous bacterial species by activating the target protein ClpP and dysregulating the physiological proteostasis within the cell. In vitro culture of the L. interrogans fortified with the ADEP impeded the spirochete growth accompanied by a more elongated morphology. The chemoactivation of the ClpP is conditional on the duration of the self-compartmentalization of each of the ClpP isoforms. The small extent (10 min) self-assembled ClpP1P2 revealed inhibition in the peptidase activity (7-fold) in the presence of the ADEP due to the self-cleavage of the ClpP subunits. On supplementation of the {beta}-casein or bovine serum albumin, the peptidase activity of the ClpP1P2 (short-incubated) got enhanced by the ADEP, while the ClpP1P2 (long-incubated) activity was retained to the same level. ADEP can also switch on the ClpP1P2 from a strict peptidase into proteolytic machinery that discerns and degrades the unfolded protein substrates autonomous of the cognate chaperone ClpX. In consensus to the most prokaryotes with the multi ClpP variants, the computational prototype of the ClpP1P2 tertiary structure infers that the hydrophobic pocket wherein the ADEPs predominantly docks are present in the ClpP2 heptamer. Additionally, the dynamic light scattering and the site-directed mutagenesis of a catalytic serine residue in either of the ClpP isoforms proposes a second interaction site for the ADEP.

microbiology↗

bioRxiv2020

Identification of radiation responsive proteins from Spleen and Intestine tissue of mice using Mass Spectrometry approach.

PurposeExposure to ionizing radiation (IR) can cause tissue damage, which is difficult to diagnose and treat as no biomarker is available for detection. We aimed to identify proteomic signature of radiation exposure (9.5Gry) in mice and to assess the utility of Podophyllotoxin extract (PTOX) in preventing radiation injury. Materials and MethodsSpleen and Small intestinal (SI) tissues were taken from control and lethally irradiated mice at different time intervals with or without pre-treatment with Podophyllotoxin extract. Proteins were identified using Mass Spectrometry and matched with Peptide Mass Fingerprinting. ResultsWe found multiple differentially expressed radiation responsive proteins from Spleen and SI tissues in irradiated mice at 24 hours and 30 days in comparison to healthy controls (p<0.05). Differentially expressed proteins like Chromosome transmission fidelity factor ano thath 18 homolog (CTF18) and Rho GTPase-activating protein from spleen and Acta_Mouse protein from SI were identified. These proteins disappeared at 48 hrs. after IR, but re-appeared after 13 days and fully recovered at 30 days in Podophyllotoxin treated group. ConclusionsSuch proteins may be useful in early detection of radiation exposure. Pre-treatment with Podophyllotoxin leads to recovery of the disappeared proteins and improved survival following exposure to irradiation.

biochemistry↗

bioRxiv2019

RRP7A links primary microcephaly to radial glial cells and dysfunction of ribosomal biogenesis, neurogenesis and ciliary resorption

Introductory paragraphPrimary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability1. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role1. Using homozygosity mapping and whole exome sequencing, we identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, which segregated with MCPH in a consanguineous family with 10 affected individuals. RRP7A is expressed in neural stem cells/radial glial cells of the developing human forebrain, and targeted mutation of Rrp7a leads to defects in both neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in processing of ribosomal RNA, resorption of primary cilia and cell cycle progression. Finally, analysis of zebrafish embryos with loss-of-function mutation in rrp7a confirmed that RRP7A depletion causes reduced brain size, impaired neurogenesis and cell proliferation as well as defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.

neuroscience↗