M C DeBey

Bio: M C DeBey is an academic researcher from Iowa State University. The author has contributed to research in topics: Porcine enzootic pneumonia & Mycoplasma hyopneumoniae. The author has an hindex of 1, co-authored 1 publications receiving 163 citations.

Ciliostasis and loss of cilia induced by Mycoplasma hyopneumoniae in porcine tracheal organ cultures.

Abstract: In vivo- and in vitro-grown Mycoplasma hyopneumoniae organisms were inoculated onto newborn piglet tracheal organ cultures to provide a model for interaction of this organism with ciliated respiratory epithelium. Ciliostasis and loss of cilia in tracheal rings were induced by M. hyopneumoniae grown in vivo and with low-passage cultures when grown in vitro. Levels of calmodulin or dehydrogenase enzymes in tracheal ring epithelium were not altered even though ciliostasis and loss of cilia induced by M. hyopneumoniae were extensive. The capacity for inducing epithelial damage diminished with in vitro passage of the organism. Attempts to induce higher-passage cultures to attach to cilia, cause ciliostasis, or cause ciliary damage by supplementation of mycoplasmal medium with porcine lung extract failed. Epithelial damage induced by M. hyopneumoniae in tracheal rings was averted by using porcine immune serum or by separating the organisms from ciliated epithelium with a 0.1-microns-pore-size membrane. Attachment, or at least close association, of M. hyopneumoniae to ciliated epithelium appeared to be necessary to induce ciliostasis and loss of cilia in this model.

Molecular Biology and Pathogenicity of Mycoplasmas

Abstract: The recent sequencing of the entire genomes of Mycoplasma genitalium and M. pneumoniae has attracted considerable attention to the molecular biology of mycoplasmas, the smallest self-replicating organisms. It appears that we are now much closer to the goal of defining, in molecular terms, the entire machinery of a self-replicating cell. Comparative genomics based on comparison of the genomic makeup of mycoplasmal genomes with those of other bacteria, has opened new ways of looking at the evolutionary history of the mycoplasmas. There is now solid genetic support for the hypothesis that mycoplasmas have evolved as a branch of gram-positive bacteria by a process of reductive evolution. During this process, the mycoplasmas lost considerable portions of their ancestors’ chromosomes but retained the genes essential for life. Thus, the mycoplasmal genomes carry a high percentage of conserved genes, greatly facilitating gene annotation. The significant genome compaction that occurred in mycoplasmas was made possible by adopting a parasitic mode of life. The supply of nutrients from their hosts apparently enabled mycoplasmas to lose, during evolution, the genes for many assimilative processes. During their evolution and adaptation to a parasitic mode of life, the mycoplasmas have developed various genetic systems providing a highly plastic set of variable surface proteins to evade the host immune system. The uniqueness of the mycoplasmal systems is manifested by the presence of highly mutable modules combined with an ability to expand the antigenic repertoire by generating structural alternatives, all compressed into limited genomic sequences. In the absence of a cell wall and a periplasmic space, the majority of surface variable antigens in mycoplasmas are lipoproteins. Apart from providing specific antimycoplasmal defense, the host immune system is also involved in the development of pathogenic lesions and exacerbation of mycoplasma induced diseases. Mycoplasmas are able to stimulate as well as suppress lymphocytes in a nonspecific, polyclonal manner, both in vitro and in vivo. As well as to affecting various subsets of lymphocytes, mycoplasmas and mycoplasma-derived cell components modulate the activities of monocytes/macrophages and NK cells and trigger the production of a wide variety of up-regulating and down-regulating cytokines and chemokines. Mycoplasma-mediated secretion of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1 (IL-1), and IL-6, by macrophages and of up-regulating cytokines by mitogenically stimulated lymphocytes plays a major role in mycoplasma-induced immune system modulation and inflammatory responses.

Interaction of Mycoplasmas With Host Cells

Abstract: The mycoplasmas form a large group of prokaryotic microorganisms with over 190 species distinguished from ordinary bacteria by their small size, minute genome, and total lack of a cell wall. Owing to their limited biosynthetic capabilities, most mycoplasmas are parasites exhibiting strict host and tissue specificities. The aim of this review is to collate present knowledge on the strategies employed by mycoplasmas while interacting with their host eukaryotic cells. Prominant among these strategies is the adherence of mycoplasma to host cells, identifying the mycoplasmal adhesins as well as the mammalian membrane receptors; the invasion of mycoplasmas into host cells including studies on the role of mycoplasmal surface molecules and signaling mechanisms in the invasion; the fusion of mycoplasmas with host cells, a novel process that raises intriguing questions of how microinjection of mycoplasma components into eukaryotic cells subvert and damage the host cells. The observations of diverse interactions of mycoplasmas with cells of the immune system and their immunomodulatory effects and the discovery of genetic systems that enable mycoplasmas to rapidly change their surface antigenic composition have been important developments in mycoplasma research over the past decade, showing that mycoplasmas possess an impressive capability of maintaining a dynamic surface architecture that is antigenically and functionally versatile, contributing to the capability of the mycoplasmas to adapt to a large range of habitats and cause diseases that are often chronic in nature.

Swine and Poultry Pathogens: the Complete Genome Sequences of Two Strains of Mycoplasma hyopneumoniae and a Strain of Mycoplasma synoviae

Abstract: This work reports the results of analyses of three complete mycoplasma genomes, a pathogenic (7448) and a nonpathogenic (J) strain of the swine pathogen Mycoplasma hyopneumoniae and a strain of the avian pathogen Mycoplasma synoviae; the genome sizes of the three strains were 920,079 bp, 897,405 bp, and 799,476 bp, respectively. These genomes were compared with other sequenced mycoplasma genomes reported in the literature to examine several aspects of mycoplasma evolution. Strain-specific regions, including integrative and conjugal elements, and genome rearrangements and alterations in adhesin sequences were observed in the M. hyopneumoniae strains, and all of these were potentially related to pathogenicity. Genomic comparisons revealed that reduction in genome size implied loss of redundant metabolic pathways, with maintenance of alternative routes in different species. Horizontal gene transfer was consistently observed between M. synoviae and Mycoplasma gallisepticum. Our analyses indicated a likely transfer event of hemagglutinin-coding DNA sequences from M. gallisepticum to M. synoviae.

Polymicrobial respiratory disease in pigs

Abstract: Respiratory disease in pigs is common in modern pork production worldwide and is often referred to as porcine respiratory disease complex (PRDC). PRDC is polymicrobial in nature, and results from infection with various combinations of primary and secondary respiratory pathogens. As a true multifactorial disease, environmental conditions, population size, management strategies and pig-specific factors such as age and genetics also play critical roles in the outcome of PRDC. While non-infectious factors are important in the initiation and outcome of cases of PRDC, the focus of this review is on infectious factors only. There are a variety of viral and bacterial pathogens commonly associated with PRDC including porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), porcine circovirus type 2 (PCV2), Mycoplasma hyopneumoniae (MHYO) and Pasteurella multocida (PMULT). The pathogenesis of viral respiratory disease is typically associated with destruction of the mucocilliary apparatus and with interference and decrease of the function of pulmonary alveolar and intravascular macrophages. Bacterial pathogens often contribute to PRDC by activation of inflammation via enhanced cytokine responses. With recent advancements in pathogen detection methods, the importance of polymicrobial disease has become more evident, and identification of interactions of pathogens and their mechanisms of disease potentiation has become a topic of great interest. For example, combined infection of pigs with typically low pathogenic organisms like PCV2 and MHYO results in severe respiratory disease. Although the body of knowledge has advanced substantially in the last 15 years, much more needs to be learned about the pathogenesis and best practices for control of swine respiratory disease outbreaks caused by concurrent infection of two or more pathogens. This review discusses the latest findings on polymicrobial respiratory disease in pigs.

Influenza virus infection decreases tracheal mucociliary velocity and clearance of Streptococcus pneumoniae.

Abstract: Influenza virus infections increase susceptibility to secondary bacterial infections, such as pneumococcal pneumonia, resulting in increased morbidity and mortality. Influenza-induced tissue damage is hypothesized to increase susceptibility to Streptococcus pneumoniae infection by increasing adherence to the respiratory epithelium. Using a mouse model of influenza infection followed by S. pneumoniae infection, we found that an influenza infection does not increase the number of pneumococci initially present within the trachea, but does inhibit pneumococcal clearance by 2 hours after infection. To determine whether influenza damage increases pneumococcal adherence, we developed a novel murine tracheal explant system to determine influenza-induced tissue damage and subsequent pneumococcal adherence. Murine tracheas were kept viable ex vivo as shown by microscopic examination of ciliary beating and cellular morphology using continuous media flow for up to 8 days. Tracheas were infected with influenza virus for 0.5–5 days ex vivo, and influenza-induced tissue damage and the early stages of repair to the epithelium were assessed histologically. A prior influenza infection did not increase pneumococcal adherence, even when the basement membrane was maximally denuded or during the repopulation of the basement membrane with undifferentiated epithelial cells. We measured mucociliary clearance in vivo and found it was decreased in influenza-infected mice. Together, our results indicate that exposure of the tracheal basement membrane contributes minimally to pneumococcal adherence. Instead, an influenza infection results in decreased tracheal mucociliary velocity and initial clearance of pneumococci, leading to an increased pneumococcal burden as early as 2 hours after pneumococcal infection.