Current Issues in Molecular Biology

2185 KiB

Open AccessReview

The Evolution of Flea-Borne Transmission in Yersinia pestis

by B. Joseph Hinnebusch

Curr. Issues Mol. Biol. 2005, 7(2), 197-212; https://doi.org/10.21775/cimb.007.197 - 2 Aug 2005

Cited by 112 | Viewed by 1712

Transmission by fleabite is a recent evolutionary adaptation that distinguishes Yersinia pestis, the agent of plague, from Yersinia pseudotuberculosis and all other enteric bacteria. The very close genetic relationship between Y. pestis and Y. pseudotuberculosis indicates that just a few discrete genetic changes were sufficient to give rise to flea-borne transmission. Y. pestis exhibits a distinct infection phenotype in its flea vector, and a transmissible infection depends on genes that are specifically required in the flea, but not the mammal. Transmission factors identified to date suggest that the rapid evolutionary transition of Y. pestis to flea-borne transmission within the last 1,500 to 20,000 years involved at least three steps: acquisition of the two Y. pestis-specific plasmids by horizontal gene transfer; and recruitment of endogenous chromosomal genes for new functions. Perhaps reflective of the recent adaptation, transmission of Y. pestis by fleas is inefficient, and this likely imposed selective pressure favoring the evolution of increased virulence in this pathogen. Full article

882 KiB

Open AccessReview

The Role of Cathelicidins in the Innate Host Defenses of Mammals

by Margherita Zanetti

Curr. Issues Mol. Biol. 2005, 7(2), 179-196; https://doi.org/10.21775/cimb.007.179 - 2 Aug 2005

Cited by 356 | Viewed by 1362

Abstract

The cathelicidin peptides comprise one of several families of antimicrobial peptides that are found in neutrophils and epithelia as components of the early host defenses of mammals against infection. All cathelicidin family members are synthesized and stored in cells as two-domain proteins. These are split on demand to produce a cathelin protein and an antimicrobial peptide. Accumulating evidence indicates that both the cathelin portion and the C-terminal peptide exert biological activities connected with host protection. This review presents an overview of the structure and biology of cathelicidins and discusses recent progress in cathelicidin research with emphasis on the functional properties and role in host defense of the human cathelicidin hCAP18/LL-37. Although investigators initially concentrated their attention on antibiotic activity, it is becoming clear now that LL-37 is a multifunctional molecule that may mediate various host responses, and thus represents an essential component of the innate immune system in humans. Full article

1868 KiB

Open AccessReview

Transcriptional Regulation in Yersinia: An Update

by Michael Marceau

Curr. Issues Mol. Biol. 2005, 7(2), 151-178; https://doi.org/10.21775/cimb.007.151 - 2 Aug 2005

Viewed by 578

Abstract

In response to the ever-present need to adapt to environmental stress, bacteria have evolved complex (and often overlapping) regulatory networks that respond to various changes in growth conditions, including entry into the host. The expression of most bacterial virulence factors is regulated; thus the question of how bacteria orchestrate this process has become a recurrent research theme for every bacterial pathogen, and the three pathogenic Yersinia are no exception. The earliest studies of regulation in these species were prompted by the characterization of plasmid-encoded virulence determinants, and those conducted since have continued to focus on the principal aspects of virulence in these pathogens. Most Yersinia virulence factors are thermally regulated, and are active at either 28 °C (the optimal growth temperature) or 37 °C (the host temperature). However, regulation by this omnipresent thermal stimulus occurs through a wide variety of mechanisms, which generally act in conjunction with (or are modulated by) additional controls for other environmental cues such as pH, ion concentration, nutrient availability, osmolarity, oxygen tension and DNA damage. Yersinia's recent entry into the genome sequencing era has given scientists the opportunity to study these regulators on a genome-wide basis. This has prompted the first attempts to establish links between the presence or absence of regulatory elements and the three pathogenic species' respective lifestyles and degrees of virulence. Full article

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Genome-Wide Screens to Identify Genes of Human Pathogenic Yersinia Species That Are Expressed during Host Infection

by Andrew J. Darwin

Curr. Issues Mol. Biol. 2005, 7(2), 135-150; https://doi.org/10.21775/cimb.007.135 - 2 Aug 2005

Viewed by 516

Abstract

An obvious goal in the study of bacteria that cause human disease is to identify the bacterial genes required for growth within the host. Historically, this has presented a significant technological challenge. However, with this goal in mind, the in vivo expression technology (IVET) and signature-tagged mutagenesis (STM) techniques were developed during the 1990s. These techniques have been used to identify virulence genes in the three human pathogenic Yersinia species, Y. enterocolitica, Y. pseudotuberculosis and Y. pestis, using variations of their mouse models of infection. In this review, each of these studies is described individually, including the pertinent details of how each was done, and a brief discussion of the genes identified. In addition, the results of these IVET and STM screens are compared, and the striking lack of overlap between the genes identified is discussed. Most of these studies were only recently published, which means that there have been few follow-up studies on some of the novel virulence genes identified. However, the Y. enterocolitica hreP, rscR and psp genes have become the subject of further studies, which are also summarized here. Finally, I briefly describe the use of the genome-wide (but not in vivo) technology, subtractive hybridization, to identify Yersinia virulence genes. Full article

754 KiB

Open AccessReview

Antimicrobial Peptides in the Oral Environment: Expression and Function in Health and Disease

by Beverly A. Dale and L. Page Fredericks

Curr. Issues Mol. Biol. 2005, 7(2), 119-134; https://doi.org/10.21775/cimb.007.119 - 2 Aug 2005

Cited by 5 | Viewed by 1107

Abstract

The oral cavity is a unique environment in which antimicrobial peptides play a key role in maintaining health and may have future therapeutic applications. Present evidence suggests that α-defensins, β-defensins, LL-37, histatin, and other antimicrobial peptides and proteins have distinct but overlapping roles in maintaining oral health and preventing bacterial, fungal, and viral adherence and infection. The expression of the inducible hBD-2 in normal oral epithelium, in contrast to other epithelia, and the apparent differential signaling in response to commensal and pathogenic organisms, provides new insights into innate immunity in this body site. Commensal bacteria are excellent inducers of hBD-2 in oral epithelial cells, suggesting that the commensal bacterial community acts in a manner to benefit the overall innate immune readiness of oral epithelia. This may have major significance for understanding host defense in the complex oral environment. Full article

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Curr. Issues Mol. Biol., Volume 7, Issue 2 (July 2005) – 5 articles

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