Michael J Gray

Michael J Gray
University of Alabama at Birmingham | UAB · Department of Microbiology

Ph.D.

About

46
Publications
8,812
Reads
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Introduction
I am interested in how bacteria respond to reactive chlorine species (RCS) and related (pseudo)hypohalous acids and the role that those responses may play in host-microbe interactions. This has led to several ongoing lines of research: • Identifying mechanisms of bacterial hypothiocyanite (HOSCN) stress respons • Exploring the role and regulation of inorganic polyphosphate in response to stress • Examining oxidative stress responses in symbiotic gut microbes
Additional affiliations
January 2016 - present
University of Alabama at Birmingham
Position
  • Professor (Assistant)
June 2010 - December 2015
University of Michigan
Position
  • PostDoc Position
July 2004 - May 2010
University of Wisconsin–Madison
Position
  • PhD Student

Publications

Publications (46)
Article
Hypochlorous acid (HOCl), the active ingredient of household bleach, is the most common disinfectant in medical, industrial, and domestic use and plays an important role in microbial killing in the innate immune system. Given the critical importance of the antimicrobial properties of chlorine to public health, it is surprising how little is known a...
Article
Full-text available
Reactive chlorine species (RCS) such as hypochlorous acid are powerful antimicrobial oxidants. Used extensively for disinfection in household and industrial settings (i.e. as bleach), RCS are also naturally generated in high quantities during the innate immune response. Bacterial responses to RCS are complex and differ substantially from the well c...
Article
Inorganic polyphosphate is a universally conserved biopolymer whose association with oxidative stress resistance has been documented in many species, but whose mode of action has been poorly understood. Here we review the recent discovery that polyphosphate functions as a protein-protective chaperone, examine the mechanisms by which polyphosphate-m...
Article
Full-text available
Bacteria synthesize inorganic polyphosphate (polyP) in response to a wide variety of stresses, and production of polyP is essential for stress response and survival in many important pathogens and bacteria used in biotechnological processes. However, surprisingly little is known about the molecular mechanisms that control polyP synthesis. We have t...
Article
Production of inorganic polyphosphate (polyP) by bacteria is triggered by a variety of different stress conditions. PolyP is required for stress survival and virulence in diverse pathogenic microbes. Previous studies have hypothesized a model for regulation of polyP synthesis in which production of the stringent response second messenger (p)ppGpp d...
Article
Hypothiocyanite and hypothiocyanous acid (OSCN ⁻ /HOSCN) are pseudohypohalous acids released by the innate immune system which are capable of rapidly oxidizing sulfur-containing amino acids, causing significant protein aggregation and damage to invading bacteria. HOSCN is abundant in saliva and airway secretions and has long been considered a highl...
Article
Many bacterial species, including Escherichia coli (E. coli) utilize the enzyme polyphosphate kinase (PPK) to synthesize polyphosphate (polyP) in response to biological stress. Multiple studies have shown that impairing PPK activity impairs bacterial pathogenicity and survival, which has made it a target for therapeutic development. Unfortunately,...
Article
Inorganic polyphosphate (polyP) is synthesized by bacteria under stressful environmental conditions and acts by a variety of mechanisms to promote cell survival. While the kinase that synthesizes polyP (PPK, encoded by the ppk gene) is well known, ppk transcription is not activated by environmental stress and little is understood about how environm...
Preprint
Full-text available
Inorganic polyphosphate (polyP) is synthesized by bacteria under stressful environmental conditions and acts by a variety of mechanisms to promote cell survival. While the kinase that synthesizes polyP (PPK, enocoded by the ppk gene) is well known, little is understood about how environmental stress signals lead to activation of this enzyme. Previo...
Article
Inorganic polyphosphate (polyP) is produced by both bacteria and their eukaryotic hosts, and it appears to play multiple important roles in the interactions between those organisms. However, the detailed mechanisms of how polyP synthesis is regulated in bacteria, and how it influences both bacterial and host biology, remain largely unexplored. In t...
Article
Neutrophils generate hypochlorous acid (HOCl) and related reactive chlorine species as part of their defence against invading microorganisms. In isolation, bacteria respond to reactive chlorine species by upregulating responses that provide defence against oxidative challenge. Key questions are whether these responses are induced when bacteria are...
Article
Full-text available
Enterobacteria, including Escherichia coli , bloom to high levels in the gut during inflammation and strongly contribute to the pathology of inflammatory bowel diseases. To survive in the inflamed gut, E. coli must tolerate high levels of antimicrobial compounds produced by the immune system, including toxic metals like copper and reactive chlorine...
Article
Bacteria synthesize inorganic polyphosphate (polyP) in response to a variety of different stress conditions. PolyP protects bacteria by acting as a protein-stabilizing chaperone, metal chelator, or regulator of protein function, among other mechanisms. However, little is known about how stress signals are transmitted in the cell to lead to increase...
Preprint
Full-text available
Bacteria synthesize inorganic polyphosphate (polyP) in response to a variety of different stress conditions. PolyP protects bacteria by acting as a protein-stabilizing chaperone, metal chelator, or regulator of protein function, among other mechanisms. However, little is known about how stress signals are transmitted in the cell to lead to increase...
Article
Full-text available
Campylobacter jejuni causes millions of human gastrointestinal infections annually, with poultry a major source of infection. Due to the emergence of multidrug resistance in C. jejuni , there is need to identify alternative ways to control this pathogen. Genes encoding the high-affinity phosphate transporter PstSCAB are highly expressed by C. jejun...
Book
Full-text available
Course materials for graduate level bacterial genetics class. Topics include: Obtaining and Analyzing Information about Genes and Proteins, Mutational Analysis, Principles of Regulation, Experimental Design, and Genetic Engineering in Microbes. Released under a Creative Commons 4.0 Non-Commercial, No Derivatives license.
Preprint
Full-text available
Campylobacter jejuni causes acute gastroenteritis world-wide and is transmitted primarily through poultry, in which it is often a commensal member of the intestinal microbiota. Previous RNASeq experiments showed that transcripts from an operon encoding a high affinity phosphate transporter (PstSCAB) of C. jejuni were among the most abundant when gr...
Article
Full-text available
Late-onset sepsis (LOS) is thought to result from systemic spread of commensal microbes from the intestines of premature infants. Clinical use of probiotics for LOS prophylaxis has varied owing to limited efficacy, reflecting an incomplete understanding of relationships between development of the intestinal microbiome, neonatal dysbiosis and LOS. U...
Article
Full-text available
Inflammatory diseases of the gut are associated with increased intestinal oxygen concentrations and high levels of inflammatory oxidants, including hydrogen peroxide (H 2 O 2 ) and hypochlorous acid (HOCl), which are antimicrobial compounds produced by the innate immune system. This contributes to dysbiotic changes in the gut microbiome, including...
Preprint
Full-text available
Inflammatory bowel diseases (IBDs) are a growing health concern and have been linked to changes in gut microbiome composition. Enterobacteria, including Escherichia coli , bloom to high levels in the gut during inflammation and strongly contribute to the pathology of IBDs. To survive in the inflamed gut, E. coli must tolerate high levels of antimic...
Preprint
Full-text available
Inflammatory diseases of the gut are associated with increased intestinal oxygen concentrations and high levels of inflammatory oxidants, including hydrogen peroxide (H 2 O 2 ) and hypochlorous acid (HOCl), which are antimicrobial compounds produced by the innate immune system. This contributes to dysbiotic changes in the gut microbiome, including...
Article
Inorganic polyphosphate (polyP) is a biological polymer found in cells from all domains of life, and is required for virulence and stress response in many bacteria. There are a variety of methods for quantifying polyP in biological materials, many of which are either labor-intensive or insensitive, limiting their usefulness. We present here a strea...
Article
Full-text available
Mesalamine serves as the gold standard in treating ulcerative colitis. However, its precise mechanism(s) of action remains unclear. Here, we show that mesalamine treatment rapidly decreases polyphosphate levels in diverse bacteria, including members of the human gut microbiome. This decrease sensitizes bacteria towards oxidative stress, reduces col...
Article
Full-text available
Organisms use molecular chaperones to combat the unfolding and aggregation of proteins. While protein chaperones have been widely studied, here we demonstrate that DNA and RNA exhibit potent chaperone activity in vitro. Nucleic acids suppress the aggregation of classic chaperone substrates up to 300-fold more effectively than the protein chaperone...
Article
Reactive chlorine species (RCS), such as hypochlorous acid (i.e., bleach) are antimicrobial oxidants produced by the innate immune system. Like many redox-regulated transcription factors, the Escherichia coli repressor NemR responds to RCS by using the reversible oxidation of highly conserved cysteines to alter its DNA binding affinity. However, ea...
Article
Full-text available
The era in which ROS (reactive oxygen species) were simply the 'bad boys of biology' is clearly over. High levels of ROS are still rightfully considered to be toxic to many cellular processes and, as such, contribute to disease conditions and cell death. However, the high toxicity of ROS is also extremely beneficial, particularly as it is used to k...
Article
Composed of up to 1,000 phospho-anhydride bond-linked phosphate monomers, inorganic polyphosphate (polyP) is one of the most ancient, conserved, and enigmatic molecules in biology. Here we demonstrate that polyP functions as a hitherto unrecognized chaperone. We show that polyP stabilizes proteins in vivo, diminishes the need for other chaperone sy...
Article
Full-text available
Background: Little is known about how bacteria sense or respond to reactive chlorine species, such as bleach. Results: NemR is a redox-regulated transcription factor which senses bleach. Conclusion: NemR controls expression of genes encoding electrophile detoxification enzymes, which increase bleach resistance. Significance: We demonstrate a...
Article
Full-text available
Despite the extensive study of the biosynthesis of the complex molecule B (cobalamin), the mechanism by which the lower ligand 5,6-dimethylbenzimidazole (DMB) is formed has remained something of a mystery. However, recent work has identified and characterized a DMB-synthase (BluB) responsible for the oxygen-dependent, single enzyme conversion of FM...
Article
The genomes of Listeria spp. encode all but one of 25 enzymes required for the biosynthesis of adenosylcobalamin (AdoCbl; coenzyme B(12) ). Notably, all Listeria genomes lack CobT, the nicotinamide mononucleotide:5,6-dimethylbenzimidazole (DMB) phosphoribosyltransferase (EC 2.4.2.21) enzyme that synthesizes the unique α-linked nucleotide N(1) -(5-p...
Article
The chemical structures of cobamides [cobalamin (Cbl)-like compounds] are the same, except for the lower ligand, which in adenosylcobalamin (AdoCbl) is 5,6-dimethylbenzimidazole, and in adenosylpseudocobalamin (AdopseudoCbl) is adenine. Why the lower ligand of cobamides varies and what the mechanism of lower ligand replacement is are long-standing...
Article
Full-text available
The genome of Rhodobacter sphaeroides encodes the components of two distinct pathways for salvaging cobinamide (Cbi), a precursor of adenosylcobalamin (AdoCbl, coenzyme B12). One pathway, conserved among bacteria, depends on a bifunctional kinase/guanylyltransferase (CobP) enzyme to convert adenosylcobinamide (AdoCbi) to AdoCbi-phosphate (AdoCbi-P)...
Article
Bacteria and archaea use distinct pathways for salvaging exogenous cobinamide (Cbi), a precursor of adenosylcobalamin (coenzyme B(12)). The bacterial pathway depends on a bifunctional enzyme with kinase and guanylyltransferase activities (CobP in aerobic adenosylcobalamin synthesizers) to convert adenosylcobinamide (AdoCbi) to AdoCbi-guanosine diph...
Article
Full-text available
NarX-NarL and NarQ-NarP are paralogous two-component regulatory systems that control Escherichia coli gene expression in response to the respiratory oxidants nitrate and nitrite. Nitrate stimulates the autophosphorylation rates of the NarX and NarQ sensors, which then phosphorylate the response regulators NarL and NarP to activate and repress targe...
Article
Full-text available
The synthesis of 5,6-dimethylbenzimidazole (DMB), the lower ligand of coenzyme B(12), has remained elusive. We report in vitro and in vivo evidence that the BluB protein of the photosynthetic bacterium Rhodospirillum rubrum is necessary and sufficient for catalysis of the O(2)-dependent conversion of FMNH(2) to DMB. The product of the reaction (DMB...
Article
The objective of this study was to evaluate the hypothesis that the dose-response relationship for Listeria monocytogenes in humans varies with genotypic lineage or subtype. The linkages between molecular subtyping data and enumeration data for L. monocytogenes subtypes in foods consumed by the at-risk population were examined to test this hypothes...
Article
Plasmid- and phage-based firefly luciferase reporter constructs were evaluated as rapid detection systems for viable Mycobacterium avium subsp. paratuberculosis (MAP). A MAP strain bearing a luciferase-encoding plasmid was detectable at 100 cells/mL in skim milk and 1000 cells/mL in whole milk. Three luciferase-encoding mycobacteriophage were evalu...
Article
Full-text available
A total of 502 Listeria monocytogenes isolates from food and 492 from humans were subtyped by EcoRI ribotyping and PCR-restriction fragment length polymorphism analysis of the virulence gene hly. Isolates were further classified into genetic lineages based on subtyping results. Food isolates were obtained through a survey of selected ready-to-eat f...
Article
The stress-responsive, alternative sigma factor sigmaB has been described in members of three Gram-positive genera, Bacillus, Listeria, and Staphylococcus. In these bacteria, sigmaB appears to play an important role in facilitating rapid adaptation to and survival in stressful environments. sigmaB activity is regulated through a complex system of p...
Article
Full-text available
Standard plate counts (SPC) and psychrotrophic plate counts (PPC) from chocolate milk samples were compared with those of unflavored milk samples plated within 24 h of processing and at 7, 10, and 14 days of storage at 6 degrees C using matched samples collected over four time periods from four milk-processing plants. Bacterial numbers within 24 h...

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Projects (2)
Project
Reactive chlorine species (RCS), including hypochlorous acid (HOCl) and reactive chloramines, are powerful antimicrobial oxidants capable of damaging many cellular components, including proteins, lipids, cofactors, and DNA, although the precise nature of the lethal damage caused by HOCl and other RCS has been a matter of extensive debate in the literature. HOCl is a common disinfectant in medical, industrial, and home settings, but RCS are also a critical natural part of the antimicrobial arsenal of neutrophils, accumulate during inflammation, and appear to be important for controlling bacterial colonization of mucosal epithelia, such as those in the gut. While recent work has made progress in understanding how lab strains of E. coli and the Gram-positive soil bacterium Bacillus subtilis sense and respond to RCS, very few labs are studying these important questions, and knowledge of how naturally occurring members of the human microbiome respond to RCS is practically nonexistent. Filling this gap in our knowledge may be particularly important for understanding how E. coli and related enterobacteria, populations of which increase dramatically in the gut during inflammatory disease, are able to outcompete health-associated members of the microbiome (e.g. lactobacilli, Bacteroides spp., or ac-tinobacteria) under those conditions.
Project
We aim to understand how bacteria control the production of inorganic polyphosphate in response to stress.