Temperature sensing and virulence regulation in pathogenic bacteria.

Pathogenic bacteria can detect a variety of environmental signals, including temperature changes. While sudden and significant temperature variations act as danger signals that trigger a protective heat-shock response, minor temperature fluctuations typically signal to the pathogen that it has moved from one environment to another, such as entering a specific niche within a host during infection. These latter temperature fluctuations are utilized by pathogens to coordinate the expression of crucial virulence factors.

Levofloxacin and Ciprofloxacin Co-Crystals with Flavonoids: Solid-State Investigation for a Multitarget Strategy against .

In this paper, we address the problem of antimicrobial resistance in the case of with a crystal engineering approach. Two antibiotics of the fluoroquinolone class, namely, levofloxacin (LEV) and ciprofloxacin (CIP), have been co-crystallized with the flavonoids quercetin (QUE), myricetin (MYR), and hesperetin (HES), resulting in the formation of four co-crystals, namely, LEV∙QUE, LEV∙MYR, LEV∙HES, and CIP∙QUE. The co-crystals were obtained from solution, slurry, or mechanochemical mixing of the reactants.

Insights into the Orchestration of Gene Transcription Regulators in .

Bacterial pathogens employ a general strategy to overcome host defenses by coordinating the virulence gene expression using dedicated regulatory systems that could raise intricate networks. During the last twenty years, many studies of , a human pathogen responsible for various stomach diseases, have mainly focused on elucidating the mechanisms and functions of virulence factors. In parallel, numerous studies have focused on the molecular mechanisms that regulate gene transcription to attempt to understand the physiological changes of the bacterium during infection and adaptation to the environmental conditions it encounters.

Targeting the Essential Transcription Factor HP1043 of : A Drug Repositioning Study.

Antibiotic-resistant bacterial pathogens are a very challenging problem nowadays. is one of the most widespread and successful human pathogens since it colonizes half of the world population causing chronic and atrophic gastritis, peptic ulcer, mucosa-associated lymphoid tissue-lymphoma, and even gastric adenocarcinoma. Moreover, it displays resistance to numerous antibiotics.

Multilayer Regulation of NHBA at Physiologically Relevant Temperatures.

Neisseria meningitidis colonizes the nasopharynx of humans, and pathogenic strains can disseminate into the bloodstream, causing septicemia and meningitis. NHBA is a surface-exposed lipoprotein expressed by all N. meningitidis strains in different isoforms.

evades neutrophil oxidative stress responses providing a safer niche for nontypeable .

and nontypeable (NTHi) are pathogenic bacteria frequently associated with exacerbation of chronic obstructive pulmonary disease (COPD), whose hallmark is inflammatory oxidative stress. Neutrophils produce reactive oxygen species (ROS) which can boost antimicrobial response by promoting neutrophil extracellular traps (NET) and autophagy. Here, we showed that induces less ROS and NET production in differentiated HL-60 cells compared to NTHi.

Targeting of Regulators as a Promising Approach in the Search for Novel Antimicrobial Agents.

Since the discovery of penicillin in the first half of the last century, antibiotics have become the pillars of modern medicine for fighting bacterial infections. However, pathogens resistant to antibiotic treatment have increased in recent decades, and efforts to discover new antibiotics have decreased. As a result, it is becoming increasingly difficult to treat bacterial infections successfully, and we look forward to more significant efforts from both governments and the scientific community to research new antibacterial drugs.

Feeling the Heat: The HrcA Transcriptional Repressor Is an Intrinsic Protein Thermosensor.

The heat-shock response, a universal protective mechanism consisting of a transcriptional reprogramming of the cellular transcriptome, results in the accumulation of proteins which counteract the deleterious effects of heat-stress on cellular polypeptides. To quickly respond to thermal stress and trigger the heat-shock response, bacteria rely on different mechanisms to detect temperature variations, which can involve nearly all classes of biological molecules. In the response to heat-shock is transcriptionally controlled by a regulatory circuit involving two repressors, HspR and HrcA.

Definition of the Binding Architecture to a Target Promoter of HP1043, the Essential Master Regulator of .

HP1043 is an essential orphan response regulator of orchestrating multiple crucial cellular processes. Classified as a member of the OmpR/PhoB family of two-component systems, HP1043 exhibits a highly degenerate receiver domain and evolved to function independently of phosphorylation. Here, we investigated the HP1043 binding mode to a target sequence in the promoter ().

Deconvolution of intergenic polymorphisms determining high expression of Factor H binding protein in meningococcus and their association with invasive disease.

Neisseria meningitidis is a strictly human pathogen and is the major cause of septicemia and meningitis worldwide. Factor H binding protein (fHbp) is a meningococcal surface-exposed lipoprotein that binds the human Complement factor H allowing the bacterium to evade the host innate immune response. FHbp is also a key antigen in two vaccines against N.

Cooperative Regulation of Heat-Shock Genes by HspR and HrcA.

The heat-shock response is defined by the transient gene-expression program that leads to the rapid accumulation of heat-shock proteins. This evolutionary conserved response aims at the preservation of the intracellular environment and represents a crucial pathway during the establishment of host-pathogen interaction. In the food-borne pathogen two transcriptional repressors, named HspR and HrcA, are involved in the regulation of the major heat-shock genes.

The HspR-Modulator CbpA Is a Multifunctional Heat-Shock Protein.

The medically important human pathogen relies on a collection of highly conserved heat-shock and chaperone proteins to preserve the integrity of cellular polypeptides and to control their homeostasis in response to external stress and changing environmental conditions. Among this set of chaperones, the CbpA protein has been shown to play a regulatory role in heat-shock gene regulation by directly interacting with the master stress-responsive repressor HspR. Apart from this regulatory role, little is known so far about CbpA functional activities.

Stress-Response: Definition of the HrcA Regulon.

Bacteria respond to different environmental stresses by reprogramming the transcription of specific genes whose proper expression is critical for their survival. In this regard, the heat-shock response, a widespread protective mechanism, triggers a sudden increase in the cellular concentration of different proteins, including molecular chaperones and proteases, to preserve protein folding and maintain cellular homeostasis. In the medically important gastric pathogen the regulation of the principal heat-shock genes is under the transcriptional control of two repressor proteins named HspR and HrcA.

Absence of Protein A Expression Is Associated With Higher Capsule Production in Staphylococcal Isolates.

is a major human pathogen, and a leading cause of soft tissue and blood stream infections. One of the causes of its success as a pathogen is the peculiar array of immune evasion factors through which the bacterium avoids host defenses, where the staphylococcal protein A (SpA) plays a major role thanks to its IgG binding activities. Moreover, SpA has recently been proposed as a promising vaccine antigen.

The Interplay between Two Transcriptional Repressors and Chaperones Orchestrates Heat-Shock Response.

The ability to gauge the surroundings and modulate gene expression accordingly is a crucial feature for the survival bacterial pathogens. In this respect, the heat-shock response, a universally conserved mechanism of protection, allows bacterial cells to adapt rapidly to hostile conditions and to survive during environmental stresses. The important and widespread human pathogen enrolls a collection of highly conserved heat-shock proteins to preserve cellular proteins and to maintain their homeostasis, allowing the pathogen to adapt and survive in the hostile niche of the human stomach.

Regulation of heat-shock genes in bacteria: from signal sensing to gene expression output.

The heat-shock response is a mechanism of cellular protection against sudden adverse environmental growth conditions and results in the prompt production of various heat-shock proteins. In bacteria, specific sensory biomolecules sense temperature fluctuations and transduce intercellular signals that coordinate gene expression outputs. Sensory biomolecules, also known as thermosensors, include nucleic acids (DNA or RNA) and proteins.

HexR Controls Glucose-Responsive Genes and Central Carbon Metabolism in Neisseria meningitidis.

Unlabelled: Neisseria meningitidis, an exclusively human pathogen and the leading cause of bacterial meningitis, must adapt to different host niches during human infection. N. meningitidis can utilize a restricted range of carbon sources, including lactate, glucose, and pyruvate, whose concentrations vary in host niches.

Global transcriptome analysis reveals small RNAs affecting Neisseria meningitidis bacteremia.

Most bacterial small RNAs (sRNAs) are post-transcriptional regulators involved in adaptive responses, controlling gene expression by modulating translation or stability of their target mRNAs often in concert with the RNA chaperone Hfq. Neisseria meningitides, the leading cause of bacterial meningitis, is able to adapt to different host niches during human infection. However, only a few sRNAs and their functions have been fully described to date.

In depth analysis of the Helicobacter pylori cag pathogenicity island transcriptional responses.

The severity of symptoms elicited by the widespread human pathogen Helicobacter pylori is strongly influenced by the genetic diversity of the infecting strain. Among the most important pathogen factors that carry an increased risk for gastric cancer are specific genotypes of the cag pathogenicity island (cag-PAI), encoding a type IV secretion system (T4SS) responsible for the translocation of the CagA effector oncoprotein. To date, little is known about the regulatory events important for the expression of a functional cag-T4SS.

The HrcA repressor is the thermosensor of the heat-shock regulatory circuit in the human pathogen Helicobacter pylori.

Bacteria exploit different strategies to perceive and rapidly respond to sudden changes of temperature. In Helicobacter pylori the response to thermic stress is transcriptionally controlled by a regulatory circuit that involves two repressors, HspR and HrcA. Here we report that HrcA acts as a protein thermometer.

FeON-FeOFF: the Helicobacter pylori Fur regulator commutates iron-responsive transcription by discriminative readout of opposed DNA grooves.

Most transcriptional regulators bind nucleotide motifs in the major groove, although some are able to recognize molecular determinants conferred by the minor groove of DNA. Here we report a transcriptional commutator switch that exploits the alternative readout of grooves to mediate opposite output regulation for the same input signal. This mechanism accounts for the ability of the Helicobacter pylori Fur regulator to repress the expression of both iron-inducible and iron-repressible genes.

A convenient and robust in vivo reporter system to monitor gene expression in the human pathogen Helicobacter pylori.

Thirty years of intensive research have significantly contributed to our understanding of Helicobacter pylori biology and pathogenesis. However, the lack of convenient genetic tools, in particular the limited effectiveness of available reporter systems, has notably limited the toolbox for fundamental and applied studies. Here, we report the construction of a bioluminescent H.