Day 1 :
Keynote Forum
Sasha Shafikhani
Rush University Medical Center, USA
Keynote: Delayed inflammatory response renders diabetic wound vulnerable to infection and microbiome shift toward pathogenic bacteria
Time : 10:35-11:15
Biography:
Sasha Shafikhani completed his undergraduate and PhD studies from University of California at Berkeley and postdoctoral studies from University of California at San Francisco. He serves on editorial board of several reputed journals. As a cellular microbiologist, his group focuses on immune dysregulation that renders diabetic wound vulnerable to infection and microbiome shift towards pathogenic bacteria. He also uses bacterial toxins to dissect epithelial cellular responses to pathogens, particularly Pseudomonas aeruginosa.
Abstract:
Enhanced bacterial infection and microbiome shift toward pathogenic bacteria are major co-morbidities that contribute to impaired healing in diabetic 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. Surprisingly, we have found that unlike chronic diabetic ulcers which suffer from persistent unresolving 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. Importantly, treatment with a pro-inflammatory chemokine jumpstarts inflammatory response 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. 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 posit 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 unresolving inflammatory state. We further propose that pro-inflammatory chemokine therapy may be used to jumpstart inflammatory response and restore antimicrobial defenses and stimulate healing in diabetic wound.
Keynote Forum
Marc G J Feuilloley
Normandy University, France
Keynote: Key role of cutaneous neuropeptides in skin-bacterial communication and virulence
Time : 11:55-12:35
Biography:
Marc G J Feuilloley has started his carrier in Cell Biology and Endocrinology an INSERM unit before tuning to Microbiology in 1996. When he joined his present research laboratory (LMSM) of which he is Director since 2008 and where he has developed Microbial Endocrinology. He is an Invited Professor at the Max Plank Institute, expert for national and international agencies. He is managing a parallel technology transfer society for cosmetic and pharmaceutical industry and is involved in the 1st world pole in cosmetic industry (Cosmetic-Valley). He is the author of 138 articles in international journals and more than 340 oral and poster communications in national and international conferences.
Abstract:
Skin is the principal neuroendocrine organ of the human body but it is also hosting its second microbial population. In skin, neuropeptides released by nerve terminals and cells diffuse in upper epidermal layers and sweat and it was recently shown that some of these peptides control skin bacteria virulence. Substance P, CGRP and Atrial Natriuretic Peptides (ANP, CNP) can be detected by bacteria between micro- and pico-molar concentrations through moonlighting (i.e. multifunctional) proteins, such as the Thermo Unstable Ribosomal Elongation Factor (EfTu), the chaperone DnaK or the amidase AmiC which are translocated to the bacterial surface through specific systems, including MscL mechanosensitive channels, and acquire environmental sensor functions. Substance P, CGRP, ANP and CNP are without effect on bacterial growth at physiological concentrations but modulate the cytotoxicity, virulence and biofilm formation activity of very different skin bacterial species, such as Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Pseudomonas fluorescens or Propionibacterium acnes. The effect of neuropeptides on bacteria is generally rapid (<5 min) but can last for days in the case of biofilm formation and leads to dramatic increases of virulence (>400%). Some of these neuropeptides, such as substance P and CGRP, have antagonistic effects. Others are only acting on one specific species, such as CGRP on S. epidermidis or have opposite actions, such as CNP on biofilm formation by S. aureus and P. acnes. The microbiote is integrating these host signals which determine its aggressivity and skin reaction. New dermo cosmetic products are now designed on this basis.
Keynote Forum
WC Yam
The University of Hong Kong, Hong Kong
Keynote: Rapid diagnosis of drug-resistant tuberculosis
Time : 12:35-13:15
Biography:
WC Yam is currently an Associate Professor in the Department of Microbiology, Faculty of Medicine from the University of Hong Kong. As a Clinical Scientist and Fellow Member of Royal College of Pathologists, he aims at rapid diagnosis of emerging infectious diseases including tuberculosis, drug resistant HIV-1, and SARS Corona virus which he had achieved major advancement for clinical application. More recently, he has been using molecular method to study drug resistant Mycobacterium tuberculosis and HIV. The studies on multi-drug resistant Mycobacterium tuberculosis and HIV-1 have included the development of Next Generation Sequencing.
Abstract:
Tuberculosis (TB) has reemerged as a global public health concern with an annual mortality of 3 millions. Coincident with the resurgence of tuberculosis, there is also an alarming increase of infections, due to multiple drug resistant tuberculosis (MDR-TB) organisms which are resistant to two or more of the first line anti-tuberculosis drugs including isoniazid and rifampicin. Recent threat has included extensively drug resistant tuberculosis (XDR-TB) defined as MDR-TB resistant to any fluoroquinolone and at least one second-line injectable drug. For rapid diagnosis of Mycobacterium tuberculosis (M. tb), Nucleic Acid Amplification assays such as PCR facilitates the adequate and timely management of antituberculosis therapy. Conventional antimycobacterial susceptibility testing remains the standard protocol to monitor drug resistant strains. More than 90% of rifampicin resistant M. tb has been shown to be caused by mutations inside the 81-bp rifampicin resistance determining region (RRDR) located in the center of the rpoB (encodes for b–subunit of the RNA polymerase) gene. In Hong Kong, PCR-sequencing of rpoB gene of M. tb isolates revealed mutations in codons D516V, H526D and S531L inside RRDR accounted for most rifampicin-resistant M. tb. PCR-sequencing also identified hotspot mutations at positions 90, 91 and 94 of gyrase A (gyrA) gene accounted for over 85% of Ofloxacin-resistant M. tb in Hong Kong. For isoniazid resistance, multiple allele-specific PCRs (MAS-PCRs) assays targeting the mutations in codon 315 of katG gene and the 15th nucleotide preceding the mabA-inhA operon successfully identified 60-75% isoniazid-resistant M. tb in clinical specimens. Using PCR-sequencing, novel mutations associated with rifampicin and Ofloxacin resistance were also identified among treatment experienced patients. Current study on massive parallel targeted sequencing (MPTS) for simultaneous prediction of drug susceptibility in Mycobacterium tuberculosis from respiratory specimens shows promising results. The cost-effectiveness of development, introduction and availability of these methods for rapid diagnostics improves public health control and early initiation of anti-tuberculosis therapy.