Characterization of Anthrolysin O, the<i>Bacillus anthracis</i>Cholesterol-Dependent Cytolysin

Shannon, Jeffrey G.; Ross, Caná L.; Koehler, Theresa M.; Rest, Richard F.

doi:10.1128/iai.71.6.3183-3189.2003

Cited by 107 publications

(111 citation statements)

References 31 publications

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“…5B) that peaked in late exponential phase. This is consistent with recent reports showing that levels of these proteins also reach their highest levels in late exponential phase (4,39,43). It is worth noting that although the major virulence factors are regulated to some extent by growth phase, this regulation is rather modest; we observed an ϳ5-fold difference between the highest and lowest expression levels.…”

Section: Resultssupporting

confidence: 93%

Formation and Composition of the Bacillus anthracis Endospore

Liu

Bergman

Thomason³

et al. 2004

J Bacteriol

192

206

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The endospores of Bacillus anthracis are the infectious particles of anthrax. Spores are dormant bacterial morphotypes able to withstand harsh environments for decades, which contributes to their ability to be formulated and dispersed as a biological weapon. We monitored gene expression in B. anthracis during growth and sporulation using full genome DNA microarrays and matched the results against a comprehensive analysis of the mature anthrax spore proteome. A large portion (ϳ36%) of the B. anthracis genome is regulated in a growth phase-dependent manner, and this regulation is marked by five distinct waves of gene expression as cells proceed from exponential growth through sporulation. The identities of more than 750 proteins present in the spore were determined by multidimensional chromatography and tandem mass spectrometry. Comparison of data sets revealed that while the genes responsible for assembly and maturation of the spore are tightly regulated in discrete stages, many of the components ultimately found in the spore are expressed throughout and even before sporulation, suggesting that gene expression during sporulation may be mainly related to the physical construction of the spore, rather than synthesis of eventual spore content. The spore also contains an assortment of specialized, but not obviously related, metabolic and protective proteins. These findings contribute to our understanding of spore formation and function and will be useful in the detection, prevention, and early treatment of anthrax. This study also highlights the complementary nature of genomic and proteomic analyses and the benefits of combining these approaches in a single study.Entry of Bacillus anthracis spores into the host from the environment, or by events brought about by human design, is the initial event of anthrax infections (8). Vegetative bacilli are not believed to be the disease contagion for any form of anthrax. The route of spore entry into the host dictates the specific pathology and severity of the disease; e.g., cutaneous anthrax is generally far less severe than either the gastrointestinal or inhalational form (8). Endospores are produced in response to nutrient deprivation via an alternative developmental cascade by two known genera of gram-positive bacteria, Clostridium and Bacillus (34). During sporulation, vegetative metabolism is minimized, and a series of alternative sigma factors are sequentially expressed and activated to coordinate the expression of mRNAs responsible for spore development (22).Mature spores are metabolically inactive and have a highly ordered structure. This structure provides the protection required for survival over long periods, even in the face of harsh environmental conditions (48). Spore germination, outgrowth, and initiation of a vegetative cycle occur when small molecules, often nutrients and/or ions, are sensed in the context of aqueous environments. B. anthracis spores recognize specific signals provided by the local environment of a mammalian host and rapidly germinate when ass...

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Section: Resultssupporting

confidence: 93%

Formation and Composition of the Bacillus anthracis Endospore

Liu

Bergman

Thomason³

et al. 2004

J Bacteriol

192

206

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“…We propose that during infection, B. anthracis secretes anthrolysin O, leading to the lysis of red blood cells (62). The released hemoglobin might serve as a source of two essential nutrients.…”

Section: Discussionmentioning

confidence: 98%

Bacillus anthracis Overcomes an Amino Acid Auxotrophy by Cleaving Host Serum Proteins

et al. 2015

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Bacteria sustain an infection by acquiring nutrients from the host to support replication. The host sequesters these nutrients as a growth-restricting strategy, a concept termed "nutritional immunity." Historically, the study of nutritional immunity has centered on iron uptake because many bacteria target hemoglobin, an abundant circulating protein, as an iron source. Left unresolved are the mechanisms that bacteria use to attain other nutrients from host sources, including amino acids. We employed a novel medium designed to mimic the chemical composition of human serum, and we show here that Bacillus anthracis, the causative agent of anthrax disease, proteolyzes human hemoglobin to liberate essential amino acids which enhance its growth. This property can be traced to the actions of InhA1, a secreted metalloprotease, and extends to at least three other serum proteins, including serum albumin. The results suggest that we must also consider proteolysis of key host proteins to be a way for bacterial pathogens to attain essential nutrients, and we provide an experimental framework to determine the host and bacterial factors involved in this process. IMPORTANCEThe mechanisms by which bacterial pathogens acquire nutrients during infection are poorly understood. Here we used a novel defined medium that approximates the chemical composition of human blood serum, blood serum mimic (BSM), to better model the nutritional environment that pathogens encounter during bacteremia. Removing essential amino acids from BSM revealed that two of the most abundant proteins in blood-hemoglobin and serum albumin-can satiate the amino acid requirement for Bacillus anthracis, the causative agent of anthrax. We further demonstrate that hemoglobin is proteolyzed by the secreted protease InhA1. These studies highlight that common blood proteins can be a nutrient source for bacteria. They also challenge the historical view that hemoglobin is solely an iron source for bacterial pathogens. There are three broad, necessary, and common elements inherent in most if not all bacterial infections of vertebrate hosts. They are (i) the initial entry of the bacterial invader and adherence to host tissues, (ii) the production of virulence factors or toxins (usually proteins) that subvert host innate and acquired immune defense mechanisms, and (iii) the acquisition and construction of biomolecules to drive cellular metabolism for the production of progeny. There has been intense investigation, and knowledge of the biochemistry, cell biology, and contribution to disease of a diverse array of bacterial adhesins and virulence factors (points i and ii identified above) is growing. However, our knowledge of nutrient acquisition during pathogenesis has lagged, perhaps because it is viewed as being a necessary and somewhat mundane process that may lack the elegant sophistication observed with virulence factors. Considering that all systemic infections are absolutely dependent on the replication of bacterial cells, identifying the mechanisms by which ba...

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“…The capsule is made up of poly-c-Dglutamic acid, that inhibits the bacterial phagocytosis during infection and is weakly immunogenic in nature [42]. Another major virulence factor is anthrolysin O, which is one of the pore forming toxins and disrupts the membrane integrity of host cells by forming homogenous pores [43]. The systemic infection of anthrax is majorly established by lethal toxin (protective antigen ?…”

Section: Bacillus Anthracismentioning

confidence: 99%

Bacterial Virulence Factors: Secreted for Survival

et al. 2016

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Virulence is described as an ability of an organism to infect the host and cause a disease. Virulence factors are the molecules that assist the bacterium colonize the host at the cellular level. These factors are either secretory, membrane associated or cytosolic in nature. The cytosolic factors facilitate the bacterium to undergo quick adaptive-metabolic, physiological and morphological shifts. The membrane associated virulence factors aid the bacterium in adhesion and evasion of the host cell. The secretory factors are important components of bacterial armoury which help the bacterium wade through the innate and adaptive immune response mounted within the host. In extracellular pathogens, the secretory virulence factors act synergistically to kill the host cells. In this review, we revisit the role of some of the secreted virulence factors of two human pathogens: Mycobacterium tuberculosis-an intracellular pathogen and Bacillus anthracis-an extracellular pathogen. The advances in research on the role of secretory factors of these pathogens during infection are discussed.

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Characterization of Anthrolysin O, theBacillus anthracisCholesterol-Dependent Cytolysin

Cited by 107 publications

References 31 publications

Formation and Composition of the Bacillus anthracis Endospore

Formation and Composition of the Bacillus anthracis Endospore

Bacillus anthracis Overcomes an Amino Acid Auxotrophy by Cleaving Host Serum Proteins

Bacterial Virulence Factors: Secreted for Survival

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