Team:XJTLU-CHINA/Description

Description

Description

What’s Our Focus?

----Intestinal S.aureus Colonization

Staphylococcus aureus is a major human pathogen that contributes to a variety of lethal diseases, causing a large burden of morbidity and mortality worldwide. Due to its great infectivity and the abuse of antibiotics, many strains have developed resistance to an array of antibiotics, in particular, methicillin resistant S. aureus (MRSA), which already becomes an acute clinical problem.

Despite the well-established risk factor of its colonization in human nose, the gastrointestinal colonization by Staphylococcus aureus is still ill-defined. The average reported detection rate of intestinal carriage is 20% for normal strains and 9% for MRSA. The high risk population is suggested to be infants, hospitalized patients with inflammatory bowel disease (IBD), patients with a history of MRSA colonization or infection, and those with poor immune system status.

Apart from severe diarrhea, fever and dehydration, it is suggested recently that transient or persistent intestinal S. aureus colonization may cause Pseudomembranous colitis, induce specific systemic immune resonses and even alter the overall structure of the human colonic microbiota and the microbial metabolic profiles. Although it’s not been thoroughly studied yet, we believe that the potential clinical impacts cannot be underestimated.

What’s Our Aim and Why?

On these concerns:
  1. The lack of clinical experience when dealing with this rare symptom;
  2. The difficulties to prevent and fully eliminate intestinal S. aureus colonization;
  3. Abuse of antibiotics and its side effects.
Aim to:
  1. Design a novel therapy to combat with, and even prevent the intestinal S. aureus colonization within a short time after infection, thus reducing the use of antibiotics and restraining the development and transmission of MRSA.
  2. 2. Introduce a new concept medicine that is safe, effective, and has the potential to be industrialized and put into drug market (which needs approval of China's State Food and Drug Administration).

How We Make it Happen?

--Probiotic Therapy

We genetically engineered Lactococcus lactis to become our drug carrier (“Grenadier Guards”), which will become active when arriving human intestine after digesting.

With a copy of the quorum sensing system from S. aureus, they will quickly sense the presence of the pathogen cells that are above the threshold concentration and have the mobility to move near the colony. Simultaneously, the synthesis of antimicrobial peptides (“Grenades”) will begin. Osmoregulation and tandem repeating are applied here to control the synthesis of our AMPs and allow them to reach a relatively high quantity level. After AMPs accumulation, our Lactococcus lactis will go through an endolysis procedure to release the synthesized peptides to attack the biofilm of S. aureus. All of these metabolism should proceed within a short time, so when combined with its large quantity and proper anti-diarrhea drugs, the symptom is likely to be reduced and even eliminated.