Abstract: AIEC-LF82 is a strain of bacteria that is surmised to have a role in causing IBD and Crohn’s disease by activating pro-inflammatory gene expression in organisms. Using antibiotics via combination therapy has been a technique used in clinical settings in an attempt to treat the strains, however, the attempts have not been that effective nor efficient in terms of completely halting the growth and colonization of AIEC to treat IBD and Crohn’s disease patients. Research has shown that regarding hindering or preventing the colonization bacterial colonies, sequential therapy tends to be more effective and time-efficient than combination therapy, with fewer adverse effects. To test if this is also the case with the AIEC-LF82 strain of bacteria, I first tested AIEC’s response to combination therapy using the Penicillin-Streptomycin, Kanamycin-Chloramphenicol, antimicrobial peptide (AMP), Kanamycin, SPE phase and LB agar plates, all of which were experimental plates other than the LB agar plate that acted as the negative control. I then tested AIEC-LF82’s response to sequential therapy using the LB+ Kan + Spe, LB + AMP + Spe, LB+ Kan/Cam + Spe, LB + P/S + Spe, LB + P/S + Kan and LB + P/S + AMP and one LB agar plate acting as the negative control. The only differences between sets a and b were the order in which the antibiotics were administered in the six aforementioned treatment sets. Ultimately, I found that set b of sequential therapy, strong-weak antibiotic treatments, was the most effective treatment but that set a regarding sequential therapy was actually the least effective of all of the treatments. In conclusion, using strong-weak sequential antibiotic therapy treatments appears to be a potentially promising option to treat patients suffering from Crohn’s disease and IBD.Introduction: AIEC is an Adherent-Invasive strain of E. Coli bacteria that is highly linked to patients with chronic Crohn’s disease and IBD. It is suspected to instigate chronic inflammation in susceptible hosts by altering gut microbiota composition, which would allow it to have a greater chance of activating pro-inflammatory gene expression. AIEC strains tend to colonize the intestinal mucosa by adhering to intestinal epithelial cells, so the important role that is played by the AIEC strain, in Crohn’s disease and IBD pathogenicity, is due to their ability to invade both intestinal epithelial cells and macrophages (4, 12). This in turn results in very high levels of secretion of pro-inflammatory cytokines, which ultimately contributes to chronic inflammation. Adherent-Invasive E.coli bacteria are also true invasive pathogens because they are able to invade intestinal epithelial cells via a macropinocytosis-like process, allowing them to be able to survive and replicate intracellularly after lysis of the endocytic vacuole (11). Inside macrophages themselves, AIEC strains survive and replicate without inducing host cell death and induce the release of high amounts of TNFα, making them a very dangerous strain of E.coli (11). These virulence properties designate AIEC as a pathogen that can potentially induce persistent intestinal inflammation by crossing and breaching the intestinal barrier, moving into deep tissues, and continuously activating macrophages to infect host cells. This led me to take the stance that the antibiotic treatments would be able to potentially prevent the AIEC bacteria from being able to colonize and thrive. This is since the infection cycle of adherent-invasive E. Coli appears to depend heavily on the ability of these bacteria to first be able to colonize in the gastrointestinal tract of genetically predisposed Crohn's disease and IBD patients (12). Another pressing issue is the emergence of mutant strains of bacteria being resistant to one or many antibiotics (9). Even though in the past multidrug treatments often reduce the prevalence of severe infections, research has shown that excessive use of antibiotics has resulted in the evolution of multidrug resistance in many species of bacteria (5). Multidrug resistance is also extremely frequent in many healthcare-associated bacterial infections, such as Staphylococcus aureus, and Pseudomonas aeruginosa which can tend to make the optimal use of multidrug therapy more difficult regarding medical treatment. Using antibiotics simultaneously for combination therapy or sequentially for sequential therapy are techniques commonly used in the healthcare industry, in which two or more different antibiotics are used one after the other. Combination therapy can be used to successfully treat Helicobacter pylori (1), which is an agent of peptic ulcers or in this case the AIEC variants of E.Coli. However, one of the flaws is that combination therapy can often be associated with uncomfortable side effects if the drugs used in combination create an adverse reaction in the organism’s body. However, unlike the previously mentioned therapy sequential therapy within a single host exposes bacterial infections to a rapid change in antibiotics. The cycling process of antibiotics via combination therapy within a hospital system can take months to years to implement, but with sequential therapy, it is possible to switch antibiotics within a single host over a matter of days (10). It is also important to note that assuming that the antibiotics chosen for sequential therapy don’t elicit no cross-resistance, the mutants that are resistant against one antibiotic are unlikely to reach high frequencies within the host before a second antibiotic is applied. Though combination therapy can prove to be very effective if the correct antibiotics are used, sequential therapy is generally a more reliable technique overall. This is because a rapid switch in antibiotic use has the potential to minimize multidrug resistance while greatly minimizing any potential negative clinical consequences of combination therapy.
