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Bacillus anthracis is a deadly pathogen that under unfavourable conditions forms highly resistant spores which enable them to survive for a long period of time. Spores of B. anthracis are transmitted through the contaminated soil or animal products and enter to the host through the skin, lungs or oral route and can cause cutaneous, injection, inhalation and gastrointestinal anthrax, respectively. The disease is caused by the toxin which is produced by them once they germinate within the host cell. Anthrax toxin is the major virulence factor which has the ability to kill the host cell. The role of protein kinases and phosphatases of B. anthracis in toxin production and other virulence related properties have also been reported. There are two vaccines, BioThrax and CYFENDUSTM, which are approved by the FDA-USA to prevent anthrax disease. Recently, anthrax toxin has also been shown to be a potential candidate for cancer therapeutics. Through present review, we aim to provide insights into sporulation, transmission and pathogenesis of B. anthracis as well as the current state of its prevention, treatment, vaccines and possible therapeutic uses in cancer.

We present a mathematical model of the dynamics of Bacillus anthracis bacteria within the lymph nodes and blood of a host, following inhalation of an initial dose of spores. We also incorporate the dynamics of protective antigen, which is the binding component of the anthrax toxin produced by the bacteria. The model offers a mechanistic description of the early infection dynamics of inhalational anthrax, while its stochastic nature allows us to study the probabilities of different outcomes (for example, how likely it is that the infection will be cleared for a given inhaled dose of spores) in order to explain dose-response data for inhalational anthrax. The model is calibrated via a Bayesian approach, using in vivo data from New Zealand white rabbit and guinea pig infection studies, enabling within-host parameters to be estimated. We also leverage incubation-period data from the Sverdlovsk 1979 anthrax outbreak to show that the model can accurately describe human time-to-symptoms data under reasonable parameter regimes. Finally, we derive a simple approximate formula for the probability of symptom onset before time t , assuming that the number of inhaled spores has a Poisson distribution.

The Centers for Disease Control and Prevention (CDC) classifies Bacillus anthracis as one of the most dangerous pathogens that may affect public health and national security. Due to its importance as a potential biological weapon, this bacteria has been classified in the highest category A, together with such pathogens as variola virus or botulinum neurotoxin. Characteristic features of this pathogen that increase its military importance are the ease of its cultivation, transport, and storage and its ability to create survival forms that are extremely resistant to environmental conditions. However, beyond bioterrorism, B. anthracis is also a naturally occurring pathogen. Anthrax outbreaks occur in livestock and wildlife, particularly in spore-contaminated regions of Africa, Asia, and North America. Spores persist for decades, leading to recurrent infections and zoonotic transmission through direct contact, inhalation, or consumption of contaminated meat. This work presents a new electrochemical method for detecting and quantifying B. anthracis in spore form using a selective immune reaction. The developed method is based on the thiol-modified electrodes that constitute the sensing element of the electrochemical system. Tests with the B. anthracis spore suspension showed that the detection limit for this pathogen is as low as 103 CFU/mL. Furthermore, it was possible to quantify the analyte with a sensitivity of 11 mV/log (CFU/mL). Due to several features, such as low unit cost, portability, and minimal apparatus demands, this method can be easily implemented in field analyzers for this pathogen and provides an alternative to currently used techniques and devices.

HPLC-UV was used to compare the major constituents of two Pelargonium × hortorum cultivars and Pelargonium sidoides root extract. It revealed the presence of catechin and gallic acid in high concentrations and the absence of umckalin in P. × hortorum root extracts. The antibacterial activity of these extracts was screened against 19 Pseudomonas aeruginosa clinical isolates. P. × hortorum root extracts showed the lowest MIC values (512–1024 µg/mL). This activity was concluded to be attributable to the high concentrations of catechin and gallic acid. The anti-biofilm activity of catechin, gallic acid, and their combination was examined by a crystal violet assay. The combination reduced the percentage of strong and moderate biofilm-forming isolates from 52.63% to 5.26%. The impact on lasI and lasR genes expression using qRT-PCR and simultaneous docking against LasR protein was explored. The combination downregulated lasI and lasR gene expression in eight and six P. aeruginosa isolates, respectively, and showed the greatest docking score. Additionally, the in vivo protection capability of this combination in infected mice showed enhancement in the survival rate. Our study revealed the potential biofilm and quorum-sensing-inhibitory activity of the catechin and gallic acid combination as a novel alternative to inhibit bacterial pathogenicity.

Clostridium difficile infection (CDI) is an important hospital-acquired infection resulting from the germination of spores in the intestine as a consequence of antibiotic-mediated dysbiosis of the gut microbiota. Key to this is CotE, a protein displayed on the spore surface and carrying 2 functional elements, an N-terminal peroxiredoxin and a C-terminal chitinase domain. Using isogenic mutants, we show in vitro and ex vivo that CotE enables binding of spores to mucus by direct interaction with mucin and contributes to its degradation. In animal models of CDI, we show that when CotE is absent, both colonization and virulence were markedly reduced. We demonstrate here that the attachment of spores to the intestine is essential in the development of CDI. Spores are usually regarded as biochemically dormant, but our findings demonstrate that rather than being simply agents of transmission and dissemination, spores directly contribute to the establishment and promotion of disease.

A study was conducted to assess the efficacy of ozone gas in inactivating spores of both Bacillus anthracis and Bacillus subtilis inoculated onto six building materials (glass, wood, carpet, laminate, galvanized metal, and wallboard paper). Testing conditions consisted of ozone gas concentrations ranging from 7,000-12,000 parts per million (ppm), contact times from 4 to 12 h, and two relative humidity (RH) levels of 75 and 85%. Results showed that increasing the ozone concentration, contact time, and RH generally increased decontamination efficacy. The materials in which the highest decontamination efficacy was achieved for B. anthracis spores were wallboard paper, carpet, and wood with ≥ 6 log10 reduction (LR) occurring with 9,800 ppm ozone, 85% RH, for 6 h. The laminate and galvanized metal materials were generally more difficult to decontaminate, requiring 12,000 ppm ozone, 85% RH, and 9-12 h contact time to achieve ≥6 LR of B. anthracis. Lastly, overall, there were no significant differences in decontamination efficacy between the two species.

Membrane proteins are fascinating since they play an important role in diverse cellular functions and constitute many drug targets. Membrane proteins are challenging to analyze. The spore, the most resistant form of known life, harbors a compressed inner membrane. This membrane acts not only as a barrier for undesired molecules but also as a scaffold for proteins involved in signal transduction and the transport of metabolites during spore germination and subsequent vegetative growth. In this study, we adapted a membrane enrichment method to study the membrane proteome of spores and cells of the food-borne pathogen Bacillus cereus using quantitative proteomics. Using bioinformatics filtering we identify and quantify 498 vegetative cell membrane proteins and 244 spore inner membrane proteins. Comparison of vegetative and spore membrane proteins showed there were 54 spore membrane-specific and 308 cell membrane-specific proteins. Functional characterization of these proteins showed that the cell membrane proteome has a far larger number of transporters, receptors and proteins related to cell division and motility. This was also reflected in the much higher expression level of many of these proteins in the cellular membrane for those proteins that were in common with the spore inner membrane. The spore inner membrane had specific expression of several germinant receptors and spore-specific proteins, but also seemed to show a preference towards the use of simple carbohydrates like glucose and fructose owing to only expressing transporters for these. These results show the differences in membrane proteome composition and show us the specific proteins necessary in the inner membrane of a dormant spore of this toxigenic spore-forming bacterium to survive adverse conditions.

In addition to their well-known role as stress-associated catecholamine hormones in animals and humans, epinephrine (EPI) and norepinephrine (NE) act as interkingdom signals between eukaryotic hosts and bacteria. However, the molecular basis of their effects on bacteria is not well understood. In initial phenotypic studies utilizing Vibrio campbellii as a model organism, we characterized the bipartite mode of action of catecholamines, which consists of promotion of growth under iron limitation and enhanced colony expansion on soft agar. In order to identify the molecular targets of the hormones, we designed and synthesized tailored probes for chemical proteomic studies. As the catechol group in EPI and NE acts as an iron chelator and is prone to form a reactive quinone moiety, we devised a photoprobe based on the adrenergic agonist phenylephrine (PE), which solely influenced colony expansion. Using this probe, we identified CheW, located at the core of the chemotaxis signaling network, as a major target. In vitro studies confirmed that EPI, NE, PE, and labetalol, a clinically applied antagonist, bind to purified CheW with affinity constants in the submicromolar range. In line with these findings, exposure of V. campbellii to these adrenergic agonists affects the chemotactic control of the bacterium. This study highlights an effect of eukaryotic signaling molecules on bacterial motility.

Pseudomonas syringae pv. coronafaciens (Ps-c) is a pathogenic bacterium species that can be found in agricultural environments and causes diseases in plants. During a survey in 2019–2020 of different areas, bacterial halo blight (BHB) caused by Ps-c in oat (Avena sativa L.) was observed in many oat fields in Huan county, Gansu Province of China. Average leaf disease incidence was approximately 1 to 14%. The symptoms of BHB were mainly observed on leaves of oat and appeared as white to yellow streaks. After 20–30 d, the streaks became yellow necrotic lesions and spread over whole leaves, eventually causing leaves to wilt and senesce. Symptomatic leaves of affected oats were collected to investigate the etiology of BHB disease. A group of 32 bacterial isolates (HK7) phenotypically similar were isolated from the necrotic lesion margins. Pathogenicity tests of this group of isolates by wounding and injection demonstrated that the symptoms induced by them on oat were similar to those observed in the field. HK7 isolates were identified as Ps-c based on Biolog Gen III MicroStation, morphological, physiological and biochemical characterization, 16S rRNA and gyrB gene sequence analysis, which compared with a reference strain (Ps-c ATCC 19608). Furthermore, Ps-c was host specific. After inoculation of Ps-c on A. sativa (B7) and A. nuda (B2) in greenhouse by Completely Randomized Design (CRD), number of tillers, plant height, flag-leaf length, flag-leaf width, fresh weight, dry weight, panicle length, grains per spike, reproductive branche number and thousand grains weight of infected oat decreased by 19.44%, 11.49%, 11.34%, 9.23%, 11.61%, 7.57%, 6.11%, 9.73%, 9.31% and 4.15% compared with that of healthy oat, respectively. BHB (Ps-c) is a new bacterial disease on oat in China and has a negative effect on plant growth, forage and grain yield of oat, and these negative effects increased with the increase of disease severity.

Sex differences in the prevalence, course and severity of infection are widespread, yet the evolutionary consequences of these differences remain unclear. Understanding how male–female differences affect the trajectory of infectious disease requires connecting the contrasting dynamics that pathogens might experience within each sex to the number of susceptible and infected individuals that are circulating in a population. In this study, we build on theory using genetic covariance functions to link the growth of a pathogen within a host to the evolution and spread of disease between individuals. Using the Daphnia–Pasteuria system as a test case, we show that on the basis of within-host dynamics alone, females seem to be more evolutionarily liable for the pathogen, with higher spore loads and greater divergence among pathogen genotypes as infection progresses. Between-host transmission, however, appears to offset the lower performance of a pathogen within a male host, making even subtle differences between the sexes evolutionarily relevant, as long as the selection generated by the between-host dynamics is sufficiently strong. Our model suggests that relatively simple differences in within-host processes occurring in males and females can lead to complex patterns of genetic constraint on pathogen evolution, particularly during an expanding epidemic. This article is part of the theme issue ‘Linking local adaptation with the evolution of sex differences’.