ABSTRACT
Keywords: biological nanomachines, multi-drug resistance, bacterial infection, bacterial evolution, conjugation, secretion systems, membrane transport, protein interactions
microorganisms infect host cells and evade therapeutic strategies. In effect, microorganisms utilize sophisticated nanomachines purpose-built for the transfer of genetic material and effector molecules. A detailed understanding of how these nanosystems are assembled from their component proteins, as well as their effects on infection and the development of resistance strategies, is critical to the development of more streamlined approaches to dealing with infection and drug resistance in pathogenic organisms.The diversity of environments in which bacteria live imposes many challenges, requiring substantial plasticity and adaptability in the genome of the organism. The interactions between bacteria, their environment and other species is an intricate interplay of diversity and adaptation in a mélange of chemical, biological and physical pressures [1]. It has been shown that in Escherichia coli sexual recombination increases rates of adaptation ~3-fold under conditions of environmental stress [2, 3]. This adaptability, while advantageous for the organism living under adverse conditions [4, 5] poses significant challenges to human health and infectious diseases, which make up ~25% of all annual deaths worldwide [6, 7]. Indeed, the recent outbreak of hemolytic uremic syndrome (HUS) linked to enterohemorrhagic Escherichia coli (EHEC) in Germany resulted in over 3500 infections leading to 50 deaths [8]. Furthermore, an outbreak of Clostridium difficile in southern Ontario, Canada, in the spring of 2011 resulted in the death of 16 patients within 6 weeks of the reported outbreak [9]. Addressing these outbreaks is becoming increasingly challenging due to the innate and acquired drug resistances that these organisms possess.It has been over 80 years since Sir Alexander Fleming gave the world its first antibiotic, penicillin [10]. During the 20 years following the introduction of penicillin, roughly half of the antibacterial drugs used today would be supplied to modern medicine [11]. In addition, between the launch of quinolones in 1962 and the US FDA approval of oxazolidnones in 2000, no new antibiotics made their way to the clinic [12]; this is truly a significant innovation gap. Overall, the rate of traditional antibiotic discovery is in decline [13], and as such, more targeted, structure-based methods have emerged to develop novel antibiotics [14-17]. However, it is becoming a trend that antibiotics, given enough time, will fail to provide the necessary means of combating microbes.
