23–5 You should not take antibiotics for diseases caused by viruses.
Discuss the following problems.
23–6 In order to survive and multiply, a successful pathogen must accomplish five tasks. Name them.
23–7 Clostridium difficile infection is the leading cause of hospital-associated gastrointestinal illness. It is typically treated with a course of antibiotics, but the infection recurs in about 20% of cases. C. difficile infections are difficult to eradicate because the bacteria exist in two forms: a replicating, toxin-producing form and a spore form that is resistant to antibiotics. Fecal microbiota transplantation—the transfer of normal gut microbiota from a healthy individual—can resolve >90% of recurrent infections, a much better cure rate than further antibiotic treatment alone. Why do you suppose microbiota transplantation is so effective?
23–8 What are the three general mechanisms for horizontal gene transfer?
23–9 The Gram-negative bacterium Yersinia pestis, the causative agent of the plague, is extremely virulent. Upon infection, Y. pestis injects a set of effector proteins into macrophages that suppresses their phagocytic behavior and also interferes with their innate immune responses. One of the effector proteins, YopJ, acetylates serines and threonines on various MAP kinases, including the MAP kinase kinase kinase TAK1, which controls a key signaling step in the innate immune response pathway. To determine how YopJ interferes with TAK1, you transfect human cells with active YopJ (YopJWT) or inactive YopJ (YopJCA) and with FLAG-tagged active TAK1 (TAK1WT) or inactive TAK1 (TAK1K63W), and assay for total TAK1 and for phosphorylated TAK1, using antibodies against the FLAG tag or against phosphorylated TAK1 (Figure Q23–1). How does YopJ block the TAK1 signaling pathway? How do you suppose the serine/threonine acetylase activity of YopJ might interfere with TAK1 activation?
IP: ˜-FLAG-TAK1 IB: ˜-pTAK1
IP: ˜-FLAG-TAK1 –76 IB: ˜-FLAG-TAK1
Figure Q23–1 effects of YopJ on TaK1 phosphorylation (Problem 23–9). TaK1 was immunoprecipitated (Ip) using antibodies against the FLaG tag (α-FLaG-TaK1). Total TaK1 in the immunoprecipitation was assayed by immunoblot (IB) using the same antibody. phosphorylated TaK1 was assayed by IB using antibodies specific for phospho-TaK1 (α-pTaK1). a scale of protein molecular mass is shown at right in kilodaltons. (From n. paquette et al., Proc. Natl Acad. Sci. USA 109:12710–12715, 2012. With permission from national academy of sciences.) 23–10 The intracellular bacterial pathogen Salmonella typhimurium, which causes gastroenteritis, injects effector proteins to promote its invasion into nonphagocytic host cells by the trigger mechanism. S. typhimurium first stimulates membrane ruffling to promote invasion, and then suppresses membrane ruffling once invasion is complete. This behavior is mediated in part by injection of two effector proteins: SopE, which promotes membrane ruffling and invasion, and SptP, which blocks the effects of SopE. Both effector proteins target the monomeric GTPase, Rac, which in its active form promotes membrane ruffling. How do you suppose SopE and SptP affect Rac activity? How do you suppose the effects of SopE and SptP are staggered in time if they are injected simultaneously?