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Volume 3 Current Research: Integrative Medicine Chronic Diseases 2018
July 16-17, 2018
Page 16
Notes:
Chronic Diseases
July 16-17, 2018 Berlin, Germany
2nd International Conference on
Sasha Shafikhani, Curr Res Integr Med 2018, Volume 3
DOI: 10.4172/2529-797X-C1-001
Molecular mechanisms underlying impaired infection control in diabetic ulcer
Enhanced bacterial infection and microbiome shift toward pathogenic bacteria are major comorbidities that contribute to
impair healing in chronic diabetic foot ulcer. The underlying reasons for the impaired infection control in diabetic wound
remain poorly understood. We used the cutaneous full-thickness wound models in STZ-injected type 1 diabetic (T1D) rats
and db/db T2D mice, to study the early dynamics of bacterial infection control in normal and diabetic wound tissues. We
have found that unlike chronic diabetic ulcers which suffer from persistent un-resolving inflammation, the acute phase of
inflammatory response which is needed to counter invading pathogens early after injury is significantly delayed in diabetic
wounds, rendering these wounds susceptible to bacterial infection and healing impairment. Our data further suggest that
normal wound tissues express pathogen-specific antimicrobial peptides (ps-AMPs) that preferentially target pathogenic bacteria
amongst commensals by recognizing specific virulence structure(s) that are only found in pathogenic bacteria. In contrast,
pathogen-specific antimicrobial defenses are impaired in diabetic wounds, thus setting the stage for the microbiome shift
toward pathogenic bacteria. We further show that the inability to control pathogenic bacteria leads to persistent inflammatory
state and impaired healing in diabetic wound. We have found that inadequate chemokine expression in diabetic wound early
after injury leads to delayed inflammatory response, which in turn results in reduced ps-AMPs, rendering diabetic wound
vulnerable to infection with pathogenic bacteria, which exacerbate wound damage and drive diabetic wound toward persistent
un-resolving inflammatory state. Importantly, we show that jumpstarting inflammatory responses in diabetic wound early
after injury resorts antimicrobial defenses and promotes healing in diabetic wound, indicating that inadequate inflammatory
response early after injury in diabetic wound is just as harmful as the persistent inflammatory state that dominates these
wounds as they become chronic.
Biography
Sasha Shafikhani has obtained his PhD from University of California at Berkeley and Postdoctoral studies from University of California at San Francisco. He is currently an
Associate Professor in the Department of Medicine at Rush University Medical Center. He serves on Editorial Board of six reputed journals. As a Cellular Microbiologist,
his group conducts projects that involve bacterial pathogenesis, cancer biology and chronic wound healing. The primary focus of his laboratory is: (i) to determine the viru-
lence mechanisms in the bacterial pathogens, particularly Pseudomonas aeruginosa; (ii) to determine the eukaryotic host responses that are intended to control bacterial
pathogen infections; and (iii) to employ bacterial toxins as molecular tools to dissect important mammalian cellular processes such as cytokinesis, apoptotic program cell
death, and apoptotic compensatory proliferation signalling.
Sasha Shafikhani
Rush University Medical Center, USA