Colony phase variation switch modulates antimicrobial tolerance and biofilm formation in .

Carbapenem-resistant causes one of the most difficult-to-treat nosocomial infections. Polycationic drugs like polymyxin B or colistin and tetracycline drugs such as doxycycline or minocycline are commonly used to treat infections caused by carbapenem-resistant . Here, we show that a subpopulation of cells associated with the opaque/translucent colony phase variation by AB5075 displays differential tolerance to subinhibitory concentrations of colistin and tetracycline.

Csu pili dependent biofilm formation and virulence of Acinetobacter baumannii.

Acinetobacter baumannii has emerged as one of the most common extensive drug-resistant nosocomial bacterial pathogens. Not only can the bacteria survive in hospital settings for long periods, but they are also able to resist adverse conditions. However, underlying regulatory mechanisms that allow A.

Insights into the genetic contexts of sulfonamide resistance among early clinical isolates of Acinetobacter baumannii.

Since the late 1930s, resistance to sulfonamides has been accumulating across bacterial species including Acinetobacter baumannii, an opportunistic pathogen increasingly implicated the spread of antimicrobial resistance worldwide. Our study aimed to explore events involved in the acquisition of sulfonamide resistance genes, particularly sul2, among the earliest available isolates of A. baumannii.

Bacterial protein MakA causes suppression of tumour cell proliferation via inhibition of PIP5K1α/Akt signalling.

Recently, we demonstrated that a novel bacterial cytotoxin, the protein MakA which is released by Vibrio cholerae, is a virulence factor, causing killing of Caenorhabditis elegans when the worms are grazing on the bacteria. Studies with mammalian cell cultures in vitro indicated that MakA could affect eukaryotic cell signalling pathways involved in lipid biosynthesis. MakA treatment of colon cancer cells in vitro caused inhibition of growth and loss of cell viability.

Emergence of high colistin resistance in carbapenem resistant in Pakistan and its potential management through immunomodulatory effect of an extract from .

Carbapenem resistant has emerged as one of the most difficult to treat nosocomial bacterial infections in recent years. It was one of the major causes of secondary infections in Covid-19 patients in developing countries. The polycationic polypeptide antibiotic colistin is used as a last resort drug to treat carbapenem resistant infections.

Metabolic and Morphotypic Trade-Offs within the Eco-Evolutionary Dynamics of Escherichia coli.

Escherichia coli arbitrarily encompasses facultative anaerobic, rod-shaped bacteria with defined respiratory and fermentative types of metabolism. The species diversification has been further advanced by atypical strains whose features deviate from the essential species-specific morphological and metabolic cutoff. The morphological cutoff is exemplified by bacterial filamentation.

Archaic chaperone-usher pili self-secrete into superelastic zigzag springs.

Adhesive pili assembled through the chaperone-usher pathway are hair-like appendages that mediate host tissue colonization and biofilm formation of Gram-negative bacteria. Archaic chaperone-usher pathway pili, the most diverse and widespread chaperone-usher pathway adhesins, are promising vaccine and drug targets owing to their prevalence in the most troublesome multidrug-resistant pathogens. However, their architecture and assembly-secretion process remain unknown.

Polar mutagenesis of polycistronic bacterial transcriptional units using Cas12a.

Background: Functionally related genes in bacteria are often organized and transcribed as polycistronic transcriptional units. Examples are the fim operon, which codes for biogenesis of type 1 fimbriae in Escherichia coli, and the atp operon, which codes for the FoF1 ATP synthase. We tested the hypothesis that markerless polar mutations could be efficiently engineered using CRISPR/Cas12a in these loci.

The gut microbiota prime systemic antiviral immunity via the cGAS-STING-IFN-I axis.

The microbiota are vital for immune homeostasis and provide a competitive barrier to bacterial and fungal pathogens. Here, we investigated how gut commensals modulate systemic immunity and response to viral infection. Antibiotic suppression of the gut microbiota reduced systemic tonic type I interferon (IFN-I) and antiviral priming.

Protein-lipid interaction at low pH induces oligomerization of the MakA cytotoxin from .

The α-pore-forming toxins (α-PFTs) from pathogenic bacteria damage host cell membranes by pore formation. We demonstrate a remarkable, hitherto unknown mechanism by an α-PFT protein from . As part of the MakA/B/E tripartite toxin, MakA is involved in membrane pore formation similar to other α-PFTs.

A tripartite cytolytic toxin formed by proteins with flagellum-facilitated secretion.

The protein MakA was discovered as a motility-associated secreted toxin from Here, we show that MakA is part of a gene cluster encoding four additional proteins: MakB, MakC, MakD, and MakE. MakA, MakB, and MakE were readily detected in culture supernatants of wild-type , whereas secretion was very much reduced from a flagellum-deficient mutant. Crystal structures of MakA, MakB, and MakE revealed a structural relationship to a superfamily of bacterial pore-forming toxins.

Teleclinical Microbiology: An Innovative Approach to Providing Web-Enabled Diagnostic Laboratory Services in Syria.

Objectives: Telemedicine can compensate for the lack of health care specialists in response to protracted humanitarian crises. We sought to assess the usability of a teleclinical microbiology (TCM) program to provide diagnostic services in a hard-to-reach region of Syria.

Methods: A semimobile station was equipped with conventional micrograph and macrograph digital imaging systems.

Ecotin and LamB in Escherichia coli influence the susceptibility to Type VI secretion-mediated interbacterial competition and killing by Vibrio cholerae.

Background: A prevailing action of the Type VI secretion system (T6SS) in several Gram-negative bacterial species is inter-bacterial competition. In the past several years, many effectors of T6SS were identified in different bacterial species and their involvement in inter-bacterial interactions were described. However, possible defence mechanisms against T6SS attack among prey bacteria were not well clarified yet.

Phosphatidic acid-mediated binding and mammalian cell internalization of the Vibrio cholerae cytotoxin MakA.

Vibrio cholerae is a noninvasive intestinal pathogen extensively studied as the causative agent of the human disease cholera. Our recent work identified MakA as a potent virulence factor of V. cholerae in both Caenorhabditis elegans and zebrafish, prompting us to investigate the potential contribution of MakA to pathogenesis also in mammalian hosts.

Suppression of β-catenin signaling in colon carcinoma cells by a bacterial protein.

Colorectal cancer is one of the leading causes of cancer-related death worldwide. The adenomatous polyposis coli (APC) gene is mutated in hereditary colorectal tumors and in more than 80% of sporadic colorectal tumors. APC mutations impair β-catenin degradation, leading to its permanent stabilization and increased transcription of cancer-driving target genes.

CRISPR-based subtyping to track the evolutionary history of a global clone of Acinetobacter baumannii.

Acinetobacter baumannii global clone 1 (GC1) is the second most common clone in the global population of A. baumannii isolates and a key cause of hospital-acquired infections. In this study, comparative analysis of the clustered regularly interspaced short palindromic repeats (CRISPR)-based sequence types (CST) was performed to determine the genetic relatedness and track patterns of descent among 187 GC1 isolates, as a complement to the evolutionary inferences from their multilocus sequence types and genome-wide single nucleotide polymorphism (SNP)-based phylogeny.

cytotoxin MakA induces noncanonical autophagy resulting in the spatial inhibition of canonical autophagy.

Autophagy plays an essential role in the defense against many microbial pathogens as a regulator of both innate and adaptive immunity. Some pathogens have evolved sophisticated mechanisms that promote their ability to evade or subvert host autophagy. Here, we describe a novel mechanism of autophagy modulation mediated by the recently discovered cytotoxin, motility-associated killing factor A (MakA).

Guideline for Urine Culture and Biochemical Identification of Bacterial Urinary Pathogens in Low-Resource Settings.

Medical diagnosis in low-resource settings is confronted by the lack of suitable guidelines, protocols and checklists. Online-accessible procedural documents are difficult to find, might be mistranslated or interpreted and usually do not address the needs of developing countries. Urinalysis, one of the most frequently performed diagnostic examinations worldwide, involves a series of tests aiming to detect particular disorders, such as urinary tract infections, kidney disease and diabetes.

Exploring the bacterial nano-universe.

Since the days of the first acknowledged microscopist, Antonie van Leeuwenhoek, the 'animalcules', that is, bacteria and other microbes have been subject to increasingly detailed visualization. With the currently most sophisticated molecular imaging method; cryo electron tomography (Cryo-ET), we are reaching the milestone of being able to image an entire organism in a single dataset at nanometer resolution. Cryo-ET will enable the next revolution in our understanding of bacterial cells, their ultra-structure and intricate molecular nanomachines.

A Cyclic-di-GMP signalling network regulates biofilm formation and surface associated motility of Acinetobacter baumannii 17978.

Acinetobacter baumannii has emerged as an increasing multidrug-resistant threat in hospitals and a common opportunistic nosocomial pathogen worldwide. However, molecular details of the pathogenesis and physiology of this bacterium largely remain to be elucidated. Here we identify and characterize the c-di-GMP signalling network and assess its role in biofilm formation and surface associated motility.

Molecular epidemiology and antimicrobial resistance features of Acinetobacter baumannii clinical isolates from Pakistan.

Background: Acinetobacter baumannii is a Gram-negative opportunistic pathogen with a notorious reputation of being resistant to antimicrobial agents. The capability of A. baumannii to persist and disseminate between healthcare settings has raised a major concern worldwide.

Absence of Global Stress Regulation in Escherichia coli Promotes Pathoadaptation and Novel c-di-GMP-dependent Metabolic Capability.

Pathoadaptive mutations linked to c-di-GMP signalling were investigated in neonatal meningitis-causing Escherichia coli (NMEC). The results indicated that NMEC strains deficient in RpoS (the global stress regulator) maintained remarkably low levels of c-di-GMP, a major bacterial sessility-motility switch. Deletion of ycgG2, shown here to encode a YcgG allozyme with c-di-GMP phosphodiesterase activity, and the restoration of RpoS led to a decrease in S-fimbriae, robustly produced in artificial urine, hinting that the urinary tract could serve as a habitat for NMEC.

Analysis of colony phase variation switch in Acinetobacter baumannii clinical isolates.

Reversible switching between opaque and translucent colony formation is a novel feature of Acinetobacter baumannii that has been associated with variations in the cell morphology, surface motility, biofilm formation, antibiotic resistance and virulence. Here, we assessed a number of phenotypic alterations related to colony switching in A. baumannii clinical isolates belonging to different multi-locus sequence types.