Martha Clokie

University of Leicester | LE · Department of Infection, Immunity and Inflammation

Tick-borne diseases are a growing concern worldwide, affecting both human and animal populations. Ticks are known to harbour a wide range of pathogens and are considered one of the most important vectors of diseases. Lyme disease, caused by Borrelia burgdorferi sensu lato, is the most common tick-borne disease in the US and Europe. However, accurat...

The environment is a natural reservoir of Clostridioides difficile and here, we aimed to isolate the pathogen from seven locations in Northern Iraq. Four of the sites yielded thirty-one isolates (ten from soils, twenty-one from sediments) which together represent ribotypes 001 (five), 010 (five), 011 (two), 035 (two), 091 (eight) and 604 (nine). Tw...

The environment is a natural reservoir of Clostridioides difficile, and here, we aimed to isolate the pathogen from seven locations in northern Iraq. Four of the sites yielded thirty-one isolates (ten from soils, twenty-one from sediments), which together represent ribotypes (RTs) 001 (five), 010 (five), 011 (two), 035 (two), 091 (eight), and 604 (...

[This corrects the article DOI: 10.3389/fmicb.2023.1166615.].

Antibiotics are frequently used in poultry production, but broad-spectrum antibiotics are problematic in driving antimicrobial resistance (AMR) within the food chain. Consequently, alternative antimicrobials are needed to treat bacterial infections and bacteriophages (phages) could provide an effective approach. Phages are natural parasites of bact...

Tick-borne diseases are a growing concern worldwide, affecting both human and animal populations. Ticks are known to harbor a wide range of pathogens and are considered one of the most important vectors of disease. Lyme disease, caused by Borrelia burgdorferi sensu lato, is the most common tick-borne disease in the US and Europe. However, accurate...

Nontyphoidal Salmonella spp. are a leading cause of human gastrointestinal infections and are commonly transmitted via consumption of contaminated meat. To limit the spread of Salmonella and other food-borne pathogens in the food chain, bacteriophage (phage) therapy could be used during rearing or pre-harvest stages of animal production. This study...

Salmonella is a food-borne pathogen often linked to poultry sources, causing gastrointestinal infections in humans, with the numbers of multidrug resistant (MDR) isolates increasing globally. To gain insight into the genomic diversity of common serovars and their potential contribution to disease, we characterized antimicrobial resistance genes, an...

Lyme disease is the most common tick-borne disease and is caused by a group of bacteria known as Borrelia burgdorferi sensu lato (s.l.) complex. Sharing the same genus as B. burgdorferi , Borrelia miyamotoi is a distinct genotype that causes relapsing fever disease. This emerging tick-borne disease is increasingly becoming a concern in public healt...

Bacteriophage (phage) therapy is a promising alternative antimicrobial strategy with the potential to transform the way bacterial infections are treated. In the United Kingdom, phages are classed as a biological medicine. Although no phages are licensed for UK use, they may be used as unlicensed medicinal products where licensed alternatives cannot...

Abstract We examined the activity of phages to control the growth of chicken and swine Salmonella strains in avian (CHIC-8E11), porcine (IPEC-1), and human (HT-29) cell cultures. We optimized a six-phage cocktail by selecting the five most effective myoviruses and a siphovirus that have optimal lysis on prevalent serovars. We observed ∼20% of 7 log...

Salmonella infections across the globe are becoming more challenging to control due to the emergence of multidrug-resistant (MDR) strains. Lytic phages may be suitable alternatives for treating these multidrug-resistant Salmonella infections. Most Salmonella phages to date were collected from human-impacted environments. To further explore the Salm...

Clostridioides difficile causes antibiotic-induced diarrhoea and pseudomembranous colitis in humans and animals. Current conventional treatment relies solely on antibiotics, but C. difficile infection (CDI) cases remain persistently high with concomitant increased recurrence often due to the emergence of antibiotic-resistant strains. Antibiotics us...

Pseudomonas aeruginosa is a notable nosocomial pathogen that can cause severe infections in humans and animals. The emergence of multidrug resistant (MDR) P. aeruginosa has motivated the development of phages to treat the infections. In this study, a novel Pseudomonas phage, vB_PaeS_VL1 (VL1), was isolated from urban sewage. Phylogenetic analyses r...

Acute non-typhoidal salmonellosis (NTS) caused by a Gram-negative bacterium Salmonella enterica serovar Typhimurium (S. Tm) is one of the most common bacterial foodborne diseases worldwide. Bacteriophages (phages) can specifically target and lyse their host bacteria, including the multidrug-resistant strains, without collateral damage to other bact...

ABSTRACT Nontyphoidal Salmonella spp. are a leading cause of human food poisoning and can be transmitted to humans via consuming contaminated pork. To reduce Salmonella spread to the human food chain, bacteriophage (phage) therapy could be used to reduce bacteria from animals’ preslaughter. We aimed to determine if adding a two-phage cocktail to fe...

Bacteriophages and phage-derived proteins are a promising class of antibacterial agents that experience a growing worldwide interest. To map ongoing phage research in Singapore and neighboring countries, Lee Kong (NUS) recently co-organized a virtual symposium on Bacter-iophage and Bacteriophage-Derived Technologies, which was attended by more than...

Bacteriophages related to phage Bp_AMP1 are the most widely spread group of phages infecting Burkholderia pseudomallei—the causative agent of melioidosis. These viruses are also infective against the nonpathogenic host Burkholderia thailandensis, allowing experimental work with them without any special safety precautions. The indirect data as well...

The characterization of therapeutic phage genomes plays a crucial role in the success rate of phage therapies. There are three checkpoints that need to be examined for the selection of phage candidates, namely, the presence of temperate markers, antimicrobial resistance (AMR) genes, and virulence genes. However, currently, no single-step tools are...

Infections caused by multidrug resistant Salmonella strains are problematic in swine and are entering human food chains. Bacteriophages (phages) could be used to complement or replace antibiotics to reduce infection within swine. Here, we extensively characterised six broad host range lytic Salmonella phages, with the aim of developing a phage cock...

Background: Fast and computationally efficient strategies are required to explore genomic relationships within an increasingly large and diverse phage sequence space. Here, we present PhageClouds, a novel approach using a graph database of phage genomic sequences and their intergenomic distances to explore the phage genomic sequence space. Methods:...

We characterized the complete genome sequence of the lytic Salmonella enterica bacteriophage PRF-SP1, isolated from Penang National Park, a conserved rainforest in northern Malaysia. The novel phage species from the Autographiviridae family has a 39,966-bp double-stranded DNA (dsDNA) genome containing 49 protein-encoding genes and shares 90.96% sim...

All known Clostridioides difficile phages encode integrases rendering them potentially able to lyse or lysogenise bacterial strains. Here, we observed the infection of the siphovirus, CDHS-1 on a ribotype 027 strain, R20291 and determined the phage and bacterial gene expression profiles, and impacts of phage infection on bacterial physiology and pa...

Introductory Paragraph Phage-bacterial recognition is species-specific, determined by interactions between phage receptor-binding proteins (RBPs) and corresponding bacterial receptors. RBPs are diverse and we present data demonstrating the identification and characterisation of a novel C. difficile phage RBP. Putative RBP were identified for CDHS-1...

This chapter discusses application of natural parasites of bacteria, bacteriophages (phages), as a promising biological control for Salmonella in poultry and swine. Many studies have shown phages can be applied at different points from farm-to-fork, from pre to post slaughter, to control the spread of Salmonella in the food chain. Pre-slaughter app...

Antimicrobial resistance (AMR) is a major problem globally. The main bacterial organisms associated with urinary tract infection (UTI) associated sepsis are E. coli and Klebsiella along with Enterobacter species. These all have AMR strains known as ESBL (Extended Spectrum Beta-Lactamase), which are featured on the WHO priority pathogens list as “cr...

The successful treatment of Lyme disease (LD) is contingent on accurate diagnosis. However, current laboratory detection assays lack sensitivity in the early stages of the disease. Because delayed diagnosis of LD incurs high healthcare costs and great suffering, new highly sensitive tests are in need. To overcome these challenges, we developed an i...

Bacteriophages offer a viable solution to addressing the global issue of bacterial resistance to antimicrobials. Although knowledge of bacteriophages has increased greatly since their discovery in 1915, a significant amount of what is currently known is based on studies conducted in model conditions and aerobic environments. There are a variety of...

Salmonella spp. is a leading cause of gastrointestinal enteritis in humans where it is largely contracted via contaminated poultry and pork. Phages can be used to control Salmonella infection in the animals, which could break the cycle of infection before the products are accessible for consumption. Here, the potential of 21 myoviruses and a siphov...

Prophages are phages that are integrated into bacterial genomes and which are key to understanding many aspects of bacterial biology. Their extreme diversity means they are challenging to detect using sequence similarity, yet this remains the paradigm and thus many phages remain unidentified. We present a novel, fast and generalizing machine learni...

The successful treatment of Lyme disease (LD) requires an accurate diagnostic test; however, most tests are insensitive and unspecific. To overcome these challenges, we developed and validated an internally-controlled quantitative PCR (Ter-qPCR) that targets the multicopy terminase large subunit ( terL ) gene encoded by prophages that are only foun...

Bacteroides spp. are part of the human intestinal microbiota but can under some circumstances become clinical pathogens. Phages are a potentially valuable therapeutic treatment option for many pathogens, but phage therapy for pathogenic Bacteroides spp. including Bacteroides fragilis is currently limited to three genome-sequenced phages. Here we de...

Bacteroides spp. are part of the human intestinal microbiota but can under some circumstances become clinical pathogens. Phages are a potentially valuable therapeutic treatment option for many pathogens, but phage therapy for pathogenic Bacteroides spp. including Bacteroides fragilis is currently limited to three genome-sequenced phages. Here we de...

The Galleria mellonella is an effective model for probing Clostridioides difficile interactions with phages. Despite valuable insights from this model, the larvae are not easily amenable to assessing detailed clinical responses to either bacteria or phages. Here, larval survival, colonisation and toxin levels were compared to expression profiles of...

This article is a summary of the activities of the ICTV’s Bacterial and Archaeal Viruses Subcommittee for the years 2018 and 2019. Highlights include the creation of a new order, 10 families, 22 subfamilies, 424 genera and 964 species. Some of our concerns about the ICTV’s ability to adjust to and incorporate new DNA- and protein-based taxonomic to...

DNA can be preserved in marine and freshwater sediments both in bulk sediment and in intact, viable resting stages. Here, we assess the potential for combined use of ancient, environmental, DNA and timeseries of resurrected long-term dormant organisms, to reconstruct trophic interactions and evolutionary adaptation to changing environments. These n...

Treatment options are limited for alcoholic hepatitis, a liver disease associated with high alcohol intake. Studies in mice reveal that the microorganisms responsible for this condition can be tackled by a viral treatment. Viral treatment tackles alcoholic hepatitis in a mouse model.

Phages are the most abundant biological entity on Earth. There are many variants in phage virion sizes, morphology, and genome sizes. Large virion sized phages, with genome sizes greater than 200 kbp have been identified and termed as Jumbo phages. These phages exhibit certain characteristics that have not been reported in phages with smaller genom...

Bacterial speciation is a fundamental evolutionary process characterized by diverging genotypic and phenotypic properties. However, the selective forces that affect genetic adaptations and how they relate to the biological changes that underpin the formation of a new bacterial species remain poorly understood. Here, we show that the spore-forming,...

A common cause of human food poisoning is through ingestion of pork products contaminated with Salmonella spp. Worryingly multi-drug resistant (MDR) Salmonella strains have been isolated from pigs, which motivates the need for alternative antimicrobials. In this study isolation and characterization of 21 lytic Salmonella phages is described. All 21...

Hypermutable loci are widespread in bacteria as mechanisms for rapid generation of phenotypic diversity within a population that enables survival of fluctuating, often antagonistic, selection pressures. Localized hypermutation can mediate phase variation and enable survival of bacteriophage predation due to high frequency, reversible alterations in...

Despite a wealth of knowledge on Salmonella phages worldwide, little is known about poultry-associated Salmonella phages from Thailand. Here, we isolated 108 phages from Thai poultry farms that infect Salmonellaenterica serovar Typhimurium. Phages STm101 and STm118 were identified as temperate Siphoviridae phages. Genome sequencing and analyses rev...

The Third Annual Meeting of the European Virus Bioinformatics Center (EVBC) took place in Glasgow, United Kingdom, 28–29 March 2019. Virus bioinformatics has become central to virology research, and advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks, being successfully used to detect, control, a...

Bacteriophage possess a variety of auxiliary metabolic genes (AMGs) of bacterial origin. These proteins enable them to maximise infection efficiency, subverting bacterial metabolic processes for the purpose of viral genome replication and synthesis of the next generation of virion progeny. Here, we examined the enzymatic activity of a cyanophage Ma...

Bacteria can use specific protein-based strategies to defend individual cells against viruses. Evidence that bacterial small molecules also target viruses provides fresh insights into how bacteria thwart viral infection.

By 2050 an estimated 10 million people will die each year from antibiotic-resistant infections — almost 90% of those in the developing world (1). Thus, alternatives to conventional antibiotics are particularly important for the developing world, with the added criteria that they must also be inexpensive, given resource limitations in low- and middl...

Melioidosis, a serious illness caused by Burkholderia pseudomallei, results in up to 40% fatality in infected patients. The pathogen is found in tropical water and soil. Recent findings demonstrated that bacterial numbers can be regulated by a novel clade of phages that are abundant in soil and water. These phages differentially infect their bacter...

Bacteriophage therapeutic development will clearly benefit from understanding the fundamental dynamics of in vivo phage-bacteria interactions. Such information can inform animal and human trials, and much can be ascertained from human cell-line work. We have developed a human cell-based system using Clostridium difficile, a pernicious hospital path...

Hypermutable loci are widespread in bacteria as mechanisms for rapid generation of phenotypic diversity, enabling individual populations to survive fluctuating, often antagonistic, selection pressures. As observed for adaptive immunity, hypermutation may facilitate survival of multiple, spatially-separated bacterial populations. We developed an ‘os...

Clostridium difficile infection (CDI) is a major cause of infectious diarrhea. Conventional antibiotics are not universally effective for all ribotypes, and can trigger dysbiosis, resistance and recurrent infection. Thus, novel therapeutics are needed to replace and/or supplement the current antibiotics. Here, we describe the activity of an optimis...

As the importance of bacteriophages as novel antimicrobials and potential diagnostics comes increasingly into focus, there is a heightened interest in understanding the mechanisms of how they interact with their bacterial hosts. The first step of a bacteriophage (phage) infection is the recognition of specific moieties on the bacterial cell surface...

The prevalence of pathogenic bacteria acquiring multidrug antibiotic resistance is a global health threat to mankind. This has motivated a renewed interest in developing alternatives to conventional antibiotics including bacteriophages (viruses) as therapeutic agents. The bacterium Clostridium difficile causes colon infection and is particularly di...