Extracellular matrix sensing via modulation of orientational order of integrins and F-actin in focal adhesions.

Specificity of cellular responses to distinct cues from the ECM requires precise and sensitive decoding of physical information. However, how known mechanisms of mechanosensing like force-dependent catch bonds and conformational changes in FA proteins can confer that this sensitivity is not known. Using polarization microscopy and computational modeling, we identify dynamic changes in an orientational order of FA proteins as a molecular organizational mechanism that can fine-tune cell sensitivity to the ECM. We find that αV integrins and F-actin show precise changes in the orientational order in an ECM-mediated integrin activation-dependent manner. These changes are sensitive to ECM density and are regulated independent of myosin-II activity though contractility can enhance this sensitivity. A molecular-clutch model demonstrates that the orientational order of integrin-ECM binding coupled to directional catch bonds can capture cellular responses to changes in ECM density. This mechanism also captures decoupling of ECM density sensing from stiffness sensing thus elucidating specificity. Taken together, our results suggest relative geometric organization of FA molecules as an important molecular architectural feature and regulator of mechanotransduction.

Corrigendum: Plasma Protein Layer Concealment Protects Streptococcus pyogenes From Innate Immune Attack.

[This corrects the article DOI: 10.3389/fcimb.2021.633394.].

Plasma Protein Layer Concealment Protects Streptococcus pyogenes From Innate Immune Attack.

Early recognition and elimination of invading pathogens by the innate immune system, is one of the most efficient host defense mechanisms preventing the induction of systemic complications from infection. To this end the host can mobilize endogenous antimicrobials capable of killing the intruder by perforating the microbial cell wall. Here, we show that Streptococcus pyogenes can shield its outer surface with a layer of plasma proteins. This mechanism protects the bacteria from an otherwise lytic attack by LL-37 and extracellular histones, allowing the bacteria to adjust their gene regulation to an otherwise hostile environment.

Monitoring and assessment of the therapeutic impact of metabolites extracted from sponge-associated bacteria screened from Gulf of Mannar, southeast coast of India.

The present study aimed to assess and monitor the therapeutic potential of antimicrobial metabolites from marine sponge-associated bacteria collected from the southeast coast of India against multidrug-resistant clinical bacterial isolates. Five sponge samples were collected and the metabolite-producing bacteria were screened from the Gulf of Mannar, India, and their antibacterial potential was studied against drug-resistant clinical bacterial isolates obtained from the hospitals. The two metabolite-producing bacteria (IS1 and IS2) were characterized by standard microbiology protocols and 16S rRNA sequencing. The antibacterial metabolites were characterized by liquid chromatography mass spectrometry (LCMS) analysis. The study suggested that marine sponges such as Spheciospongia spp., Haliclona spp., Mycale spp., Tedania spp., and SS-01 were associated with 30 ± 2, 26 ± 2, 23 ± 3, 21 ± 2, and 20 ± 2% of antibacterial metabolite-producing bacteria, respectively. The LCMS analysis of metabolites extracted from IS1 (4,6-dimethyl-2-pyrimidinamine; 4,5-dimethyl-2-propylsilyl-1H-imidazole) and IS2 (caproyl amide, 2-imidazoline) associated with Spheciospongia spp. exhibited significant antibacterial properties against drug-resistant bacteria. IS1 showed antimicrobial potential against the clinical isolates of Proteus spp., and IS2 showed antibacterial potential against isolates of both Proteus mirabilis and Salmonella typhi. IS1 and IS2 were identified by 16S rRNA sequencing and designated as Klebsiella spp. DSCE-bt01 and Pseudomonas spp. DSCE-bt02, respectively. The current study concluded that the assessment and monitoring of novel isolates from sponge-associated bacteria from marine coastal areas probably offer latest breakthrough in curtailing the global antimicrobial resistance and the study of such ecosystems adds value addition to the searching of novel bioactive compounds from terrestrial ecosystems.

Recent Aspects on the Pathogenesis Mechanism, Animal Models and Novel Therapeutic Interventions for Middle East Respiratory Syndrome Coronavirus Infections.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging zoonotic virus considered as one of the major public threat with a total number of 2 298 laboratory-confirmed cases and 811 associated deaths reported by World Health Organization as of January 2019. The transmission of the virus was expected to be from the camels found in Middle Eastern countries via the animal and human interaction. The genome structure provided information about the pathogenicity and associated virulent factors present in the virus. Recent studies suggested that there were limited insight available on the development of novel therapeutic strategies to induce immunity against the virus. The severities of MERS-CoV infection highlight the necessity of effective approaches for the development of various therapeutic remedies. Thus, the present review comprehensively and critically illustrates the recent aspects on the epidemiology of the virus, the structural and functional features of the viral genome, viral entry and transmission, major mechanisms of pathogenesis and associated virulent factors, current animal models, detection methods and novel strategies for the development of vaccines against MERS-CoV. The review further illustrates the molecular and computational virtual screening platforms which provide insights for the identification of putative drug targets and novel lead molecules toward the development of therapeutic remedies.

Recent perspectives on the molecular basis of biofilm formation by Pseudomonas aeruginosa and approaches for treatment and biofilm dispersal.

Pseudomonas aeruginosa, a Gram-negative, rod-shaped bacterium causes widespread diseases in humans. This bacterium is frequently related to nosocomial infections such as pneumonia, urinary tract infections (UTIs) and bacteriaemia especially in immunocompromised patients. The current review focuses on the recent perspectives on biofilms formation by these bacteria. Biofilms are communities of microorganisms in which cells stick to each other and often adhere to a surface. These adherent cells are usually embedded within a self-produced matrix of extracellular polymeric substance (EPS). Pel, psl and alg operons present in P. aeruginosa are responsible for the biosynthesis of extracellular polysaccharide which plays an important role in cell surface interactions during biofilm formation. Recent studies suggested that cAMP signalling pathway, quorum-sensing pathway, Gac/Rsm pathway and c-di-GMP signalling pathway are the main mechanism that leads to the biofilm formation. Understanding the bacterial virulence depends on a number of cell-associated and extracellular factors and is very essential for the development of potential drug targets. Thus, the review focuses on the major genes involved in the biofilm formation, the state of art update on the biofilm treatment and the dispersal approaches such as targeting adhesion and maturation, targeting virulence factors and other strategies such as small molecule-based inhibitors, phytochemicals, bacteriophage therapy, photodynamic therapy, antimicrobial peptides and natural therapies and vaccines to curtail the biofilm formation by P. aeruginosa.