the previous chapter, some unusual lower animal models were mentioned. Caenorhabditis elegans (worms) and Drosophila (flies) are not very useful for studies of skin infections, because the “skin” of these organisms is chitinous rather than epithelial. The zebra fish is a better model, especially for studies of the mucosal defenses. More recently, infection models have been developed based on tissues from, for example, chicken embryos. Rodents have been widely used to investigate pathogens, such as Salmonella, that bind to the intestinal mucosa. In rodents, these pathogens can sometimes cause more invasive infections than they cause in humans, but the interaction between the bacteria and the mucosa can nonetheless be followed even in these cases. A rodent model has been developed in which autoclaved feces, inoculated only with the bacterium of interest, are implanted in the intra-abdominal area of the rodent to mimic the effects of surgical penetration of the colonic mucosa.
The impact of toxins, such as diarrhea-causing toxins, on the small intestine can be monitored by the rabbit ileal loop model (Figure 2-10). In this model, the small intestine of an anesthetized rabbit is tied off into 5- to 10-cm sections by suture, the toxin or toxin-producing bacterium is injected into one of the sections (loops), and the organ is placed back into the peritoneal cavity. Many diarrheal toxins cause water to be lost by the intestinal tissues into the lumen of the gut, and this can be observed by a swelling of the section into which the toxin was injected. After 12 to 24 hours, the animal is sacrificed and the loop length and fluid volume (in ml/cm) are measured as readout. Distension (i.e., swelling) of the ileal loop section indicates release of the fluid into the lumen of the segment as a result of toxin action.
Figure 2-10. The rabbit ileal loop model of diarrheal disease. Shown are tied-off segments (loops) of rabbit ileal injected with culture filtrates from an E. coli strain producing cholera-like toxin that induces diarrhea. Loop 1 was injected with positive control solution of cholera toxin, loop 2 with negative control solution of phosphate-buffered saline, and loops 3 through 6 with increasing amounts of E. coli culture filtrates. After overnight exposure in the animal, the animal is sacrificed and the ileal loops are removed and examined for distension (swelling). Reproduced from Sack RB. 2011. Indian J Med Res 133:171–180, with permission.
Genetically engineered mice called transgenic mice or knockout mice are being increasingly used in experiments to probe the interaction of the normal microbiota and the intestinal mucosal cells because they have genes that have been altered or disrupted. Unexpectedly, some of the mice designed originally for studies of the immune system that were missing genes encoding the cytokines, interleukins IL-1 and IL-10 (see chapter 3), proved to be good models for a type of intestinal inflammation called inflammatory bowel disease (IBD). The presence of the normal bacterial microbiota of the colon seems to be responsible for the inflammatory bowel condition seen in some of these mice.
These examples are given to provide an introduction to the types of animal models that are available for studying the protective features of skin and mucosa and the consequences of breaching these barriers. Additional animal models used in connection with studying bacterial diseases, as well as alternatives to animal models such as mammalian host cells cultured in vitro in the laboratory, will be described in chapter 8 and other chapters covering specific types of infectious diseases.
SELECTED READINGS
Bik EM, Eckburg PB, Gill SR, Nelson KE, Purdom EA, Francois F, Perez-Perez G, Blaser MJ, Relman DA. 2006. Molecular analysis of the bacterial microbiota in the human stomach. Proc Natl Acad Sci USA 103:732–737.[PubMed][CrossRef]
Cooper GM, Hausman RE. 2007. The Cell—A Molecular Approach, 4th ed. ASM Press, Washington, DC.
Hooper LV. 2004. Bacterial contributions to mammalian gut development. Trends Microbiol 12:129–134.[PubMed][CrossRef]
Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI. 2001. Molecular analysis of commensal host-microbial relationships in the intestine. Science 291:881–884.[PubMed][CrossRef]
Mirmonsef P, Spear GT. 2014. The barrier to HIV transmission provided by genital tract Lactobacillus colonization. Am J Reprod Immunol 71:531–536.[PubMed][CrossRef]
Mukherjee S, Hooper LV. 2015. Antimicrobial defense of the intestine. Immunity 42:28–39.[PubMed][CrossRef]
Pronovost P, Needham D, Berenholtz S, Sinopoli D, Chu H, Cosgrove S, Sexton B, Hyzy R, Welsh R, Roth G, Bander J, Kepros J, Goeschel C. 2006. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 355:2725–2732.[PubMed][CrossRef]
Salemi C, Canola MT, Eck EK. 2002. Hand washing and physicians: how to get them together. Infect Control Hosp Epidemiol 23:32–35.[PubMed][CrossRef]
Servin AL. 2004. Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens. FEMS Microbiol Rev 28:405–440.[PubMed][CrossRef]
Strober W. 2006. Immunology. Unraveling gut inflammation. Science 313:1052–1054. [Review of an article in the same issue of the journal.][PubMed][CrossRef]
Toke O. 2005. Antimicrobial peptides: new candidates in the fight against bacterial infections. Biopolymers 80:717–735.[PubMed][CrossRef]
Winslow EH, Jacobson AF. 2000. Can a fashion statement harm the patient? Long and artificial nails may cause nosocomial infections. Am J Nurs 100:63–65.[PubMed]
Questions
1. In what sense are S. epidermidis infections an example of how changing human practices can provide new opportunities for bacterial pathogens? S. epidermidis is classified as an opportunist. Why is this the case?
2. Explain why infections of the skin occur more often in folds of the