Publications by authors named "Clayton Caswell"

Biofilms reduce antibiotic efficacy and lead to complications and mortality in human and equine patients with orthopedic infections. Equine bone marrow-derived mesenchymal stromal cells (MSC) kill planktonic bacteria and prevent biofilm formation, but their ability to disrupt established orthopedic biofilms is unknown. Our objective was to evaluate the ability of MSC to reduce established S.

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Unlabelled: SSR42 is the longest noncoding RNA in the cell and the second-most abundant transcript in the stationary phase transcriptome, second only to RNAIII. It is highly conserved across strains and exhibits pronounced stability in stationary phase, however the mechanism behind its regulatory role has yet to be fully elucidated. Herein, we used transcriptomic and proteomic approaches to probe the role of SSR42, revealing that it is a powerful, novel activator of the primary leukocidin LukAB.

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Brucella abortus is a facultative, intracellular, zoonotic pathogen that resides inside macrophages during infection. This is a specialized niche where B. abortus encounters various stresses as it navigates through the macrophage.

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Article Synopsis
  • Bacteria from the genus Brucella cause brucellosis, a serious disease affecting both animals and humans, and have been controversially merged with other unrelated bacterial species based on genomic findings.
  • Researchers argue this merger is inappropriate due to lack of thorough phylogenetic analysis and exclusion of expert opinions in brucellosis.
  • They warn that combining these groups could lead to confusion and risks in public health, particularly impacting those dealing with brucellosis in under-resourced regions, and call for keeping the Brucella genus distinct.
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Small RNAs (sRNA), in association with the global chaperone regulator Hfq, positively or negatively regulate gene expression in bacteria. For this study, Histophilus somni sRNAs that bind to Hfq were identified and then partially characterized. The Hfq-associated sRNAs in H.

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spp. are Gram-negative bacteria that naturally infect a variety of domesticated and wild animals, often resulting in abortions and sterility. Humans exposed to these animals or animal products can also develop debilitating, flu-like disease.

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Vaccination remains critical for viral disease outbreak prevention and control, but conventional vaccine development typically involves trade-offs between safety and immunogenicity. We used a recently discovered insect-specific flavivirus as a vector in order to develop an exceptionally safe, flavivirus vaccine candidate with single-dose efficacy. To evaluate the safety and efficacy of this platform, we created a chimeric Zika virus (ZIKV) vaccine candidate, designated Aripo/Zika virus (ARPV/ZIKV).

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Brucellosis is a zoonotic disease caused by a Gram-negative coccobacillus. There are four strains of zoonotic importance in our domestic species, subdivided by their culture phenotypes: (), (smooth strains) and (rough strain). Dogs can serve as hosts for all four of the zoonotic strains; however, routine serologic testing in dogs has been limited to the identification of antibodies.

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is a zoonotic pathogen that causes brucellosis. Because of unique LPS layer and intracellular localization predominately within macrophages, it can often evade immune detection. However, pattern recognition receptors are capable of sensing pathogen-associated molecular patterns (PAMPS).

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LysR-type transcriptional regulators (LTTRs) are the most common type of transcriptional regulators in prokaryotes and function by altering gene expression in response to environmental stimuli. In the class Alphaproteobacteria, a conserved LTTR named VtlR is critical to the establishment of host-microbe interactions. In the mammalian pathogen Brucella abortus, VtlR is required for full virulence in a mouse model of infection, and VtlR activates the expression of abcR2, which encodes a small regulatory RNA (sRNA).

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The neurotransmitter gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the human brain; however, it is becoming more evident that this non-proteinogenic amino acid plays multiple physiological roles in biology. In the present study, the transport and function of GABA is studied in the highly infectious intracellular bacterium Brucella abortus. The data show that 3H-GABA is imported by B.

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RNases are key regulatory components in prokaryotes, responsible for the degradation and maturation of specific RNA molecules at precise times. Specifically, RNases allow cells to cope with changes in their environment through rapid alteration of gene expression. To date, few RNases have been characterized in the mammalian pathogen In the present work, we sought to investigate several RNases in and determine what role, if any, they have in pathogenesis.

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Single-strand specific endoribonuclease YbeY has been shown to play an important role in the processing of the 3' end of the 16S rRNA in Escherichia coli. Lack of YbeY results in the accumulation of the 17S rRNA precursor. In contrast to a previous report, we show that Sinorhizobium meliloti YbeY exhibits endoribonuclease activity on single-stranded RNA substrate but not on the double-stranded substrate.

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Article Synopsis
  • The mtDNA 3243A > G mutation results in different clinical conditions based on the level of heteroplasmy: high levels lead to MELAS syndrome, while low levels are linked to MIDD syndrome.
  • Despite similarities in energy metabolic gene expression, cells with high or low heteroplasmy show significant differences in mitochondrial functions compared to normal cells.
  • Low heteroplasmic cells enhance transcription factors related to mitochondrial biogenesis and metabolism pathways, which are not present in high heteroplasmic cells, suggesting a mechanism for how low mtDNA levels may lead to diabetes.
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Brucella spp. are bacteria that naturally infect a variety of domesticated and wild animals leading to abortions and infertility, and these bacteria are also capable of causing debilitating human infections, which often result from human exposure to infected animals and animal products. The brucellae are intracellular pathogens that reside in host cells, including macrophages and dendritic cells, and it is paramount for the pathogenesis of Brucella that the bacteria are able to survive and replicate in these host cells.

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Metals are essential micronutrients for virtually all forms of life, but metal acquisition is a double-edged sword, because high concentrations of divalent cations can be toxic to the cell. Therefore, the genes involved in metal acquisition, storage and efflux are tightly regulated. The present study characterizes a nickel-responsive transcriptional regulator in the intracellular mammalian pathogen, Brucella abortus.

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Elucidating the function of proteins <50 amino acids in length is no small task. Nevertheless, small proteins can play vital roles in the lifestyle of bacteria and influence the virulence of pathogens; thus, the investigation of the small proteome is warranted. Recently, our group identified the protein VtlR as a transcriptional activator of four genes, one of which is the well-studied small regulatory RNA AbcR2, while the other three genes encode hypothetical small proteins, two of which are highly conserved among the order This study provides evidence that all three genes encode authentic small proteins and that all three are highly expressed under oxidative stress, low-pH, and stationary-phase growth conditions.

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The YbeY endoribonuclease is one of the best-conserved proteins across the kingdoms of life. In the present study, we demonstrated that YbeY in is linked to a variety of important activities, including proper cellular morphology, mRNA transcript levels, and virulence. Deletion of in led to a small-colony phenotype when the bacteria were grown on agar medium, as well as to significant aberrations in the morphology of the bacterial cell as evidenced by electron microscopy.

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The AbcR small RNAs (sRNAs) are a fascinating example of two highly conserved sRNAs that differ tremendously at the functional level among organisms. From their transcriptional activation to their regulatory capabilities, the AbcR sRNAs exhibit varying characteristics in three well-studied bacteria belonging to the Rhizobiales order: the plant symbiont Sinorhizobium meliloti, the plant pathogen Agrobacterium tumefaciens, and the animal pathogen Brucella abortus. This review outlines the similarities and differences of the AbcR sRNAs between each of these organisms, and discusses reasons as to why this group of sRNAs has diverged in their genetic organization and regulatory functions across species.

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Proline utilization (Put) systems have been described in a number of bacteria; however, the importance and functionality of the Put system in the intracellular pathogen Brucellaabortus has not been explored. Generally, bacterial Put systems are composed of the bifunctional enzyme proline dehydrogenase PutA and its transcriptional activator PutR. Here, we demonstrate that the genes putA (bab2_0518) and putR (bab2_0517) are critical for the chronic infection of mice by B.

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In , two small RNAs (sRNAs), AbcR1 and AbcR2, are responsible for regulating transcripts encoding ABC-type transport systems. AbcR1 and AbcR2 are required for virulence, as a double chromosomal deletion of both sRNAs results in attenuation in mice. Although these sRNAs are responsible for targeting transcripts for degradation, the mechanism utilized by the AbcR sRNAs to regulate mRNA in has not been described.

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Small regulatory RNAs (sRNAs) of Shigella dysenteriae and other pathogens are vital for the regulation of virulence-associated genes and processes. Here, we characterize RyfA1, one member of a sibling pair of sRNAs produced by S. dysenteriae.

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Aberrant inflammation is a hallmark of inflammatory bowel disease (IBD) and colorectal cancer. IRAK-M is a critical negative regulator of TLR signaling and overzealous inflammation. Here we utilize data from human studies and Irak-m mice to elucidate the role of IRAK-M in the modulation of gastrointestinal immune system homeostasis.

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Brucellosis is a bacterial infectious disease affecting a wide range of mammals and a neglected zoonosis caused by species of the genetically homogenous genus . As in most studies on bacterial diseases, research in brucellosis is carried out by using reference strains as canonical models to understand the mechanisms underlying host pathogen interactions. We performed whole genome sequencing analysis of the reference strain 2308 routinely used in our laboratory, including manual curated annotation accessible as an editable version through a link at https://en.

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The streptococcal collagen-like proteins 1 and 2 (Scl1 and Scl2) are major surface adhesins that are ubiquitous among group A Streptococcus (GAS). Invasive M3-type strains, however, have evolved two unique conserved features in the scl1 locus: (i) an IS1548 element insertion in the scl1 promoter region and (ii) a nonsense mutation within the scl1 coding sequence. The scl1 transcript is drastically reduced in M3-type GAS, contrasting with a high transcription level of scl1 allele in invasive M1-type GAS.

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