The Bacteriocins: Current Knowledge and Future Prospects
"a comprehensive survey" (ASM: Small Things Considered)
"an abundance of information" (BioSpektrum)
"excellent book" (Micro. Today)
Caister Academic Press
Robert L. Dorit1
, Sandra M. Roy2
and Margaret A. Riley2
1Department of Biological Sciences, Smith College - Ford Hall, Massachusetts, USA; 2Department of Biology, University of Massachusetts, Amherst, USA
xiv + 158
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Bacteriocins are potent protein toxins produced by virtually every bacterial and archeal species examined to date. These bactericidal peptides play an important role in regulating competitive interactions in natural microbial systems. From the perspective of human health, the bacteriocins represent a library of potential lead compounds honed over three billion years of evolution. Their narrow target range, high activity, surprising stability and low toxicity position them as viable alternatives or complements to existing small molecule antibiotics. The rise of antibiotic resistant pathogens and the growing awareness of the importance of the microbiome to human health underscore the need for this new class of antimicrobials, emblematic of a new approach to the treatment of infectious disease.
In this volume, a range of experts explore our current understanding of the biology of these important compounds, and identify the prospects for their use in medical and veterinary applications. In so doing, this volume introduces the vast diversity of bacteriocin molecules and mechanisms and brings readers to the cutting edge of a new 21st century approach to antibiotic discovery and design. Topics covered include: the natural history of bacteriocins; killing strategies and applications of microcins; the mode of action of nuclease colicins; the role of the van der Waals zone in the design of a new family of bacteriocins; the use of pyocins in the treatment of infections; the role of streptococccal bacteriocins as oral probiotics; veterinary applications of bacteriocins (nisin) in treating mastitis, and an exploration of the genetics of bacteriocin resistance.
This volume is essential reading for everyone involved in antimicrobial research in academia, biotechnology companies, and the pharmaceutical industry and a recommended volume for all microbiology libraries.
"a comprehensive survey across the current knowledge on these antimicrobial compounds ... a useful addition to microbiology, medical, or ecological reference libraries" from ASM: Small Things Considered
"The book offers an abundance of information" from BioSpektrum
"This excellent book summarises the current state of play as regards our understanding of a wide range of bacteriocin biology ... explores current efforts to develop bacteriocins as alternatives to traditional small molecule antibiotics ... neatly summarises our current understanding of the molecular basis of bacteriocin selectivity and potency at the molecular level, our understanding of bacteriocin ecology and evolution, and how this information is currently being used to develop bacteriocins as useful therapeutics. This book will therefore be of interest to anyone interested in the future development of antibiotics." from Microbiology Today
Table of contents
1. The Natural History of Bacteriocins
David M. Gordon
A variety of empirical and theoretical studies have demonstrated the significant role that the production of alleopathic compounds known as bacteriocins play in mediating inter- and intra-specific interactions among bacteria, and hence in shaping bacterial community diversity. There is also increasing recognition that bacteriocins may provide viable alternatives to traditional antibiotics and are a likely to be a key characteristic of probiotic strains used to prevent or limit the establishment of diarrheal pathogens. The goal of this chapter is to highlight some potentially important factors, genetic and environmental, that influence the likelihood that bacteriocin production will actually confer a fitness advantage to the producing strains and that also influence the type of bacteriocin being produced. The applied use of bacteriocins requires understanding why the production of multiple bacteriocins by a single strain is such a common phenomena in species like Esherichia coli. Finally, much of our understanding of the ecological role of bacteriocins comes from studies of the colicins released as a consequence of cell lysis, but all microcins and many colicins are secreted from the cell, and some experimental evidence is presented that would suggest we have a very incomplete understanding of the dynamics of the secreted bacteriocins.
2. Microcins and Other Bacteriocins: Bridging the Gaps Between Killing Stategies, Ecology and Applications
Bacteriocins are ribosomally-synthesized antimicrobial peptides or proteins produced by bacteria, which use these potent weapons to thrive in the microbial wars. To complete this arsenal, bacteriocin-producing strains are endowed with efficient strategies to evade being killed by their own toxins. Most bacteriocins are active in the pico- or nanomolar range and target bacterial species that are phylogenetically close to the producing strain, although some exhibit broader spectra of activity. Bacteriocins have been widely studied in Gram-positive- (lantibiotics, pediocin-like bacteriocins) and Gram-negative bacteria (colicins, microcins). However, it is becoming increasingly apparent that bacteriocin production is widespread in nature, including in the archaea, which produce similar defense proteins, the archaeocins. Bacteriocins can differ significantly both in in size and in chemical properties, ranging from small peptides (the Gram-positive bacteriocins and microcins are peptides below 10 kDa) to large proteins (colicins are 30-80 kDa proteins). Many are post-translationally modified using dedicated enzymes, leading to highly complex peptide-derived structures. This structural diversity is associated with complex and refined killing strategies, which contribute to the ecological roles of bacteriocins. Here we review these different aspects, bridging the gaps between biosynthesis, killing strategies, ecology and potential future applications.
3. Nuclease Colicins: Mode of Action, Immunity and Mechanism of Import into Escherichia coli
Justyna A. Wojdyla, Grigorios Papadakos and Colin Kleanthous
Colicins were the first bacteriocins to be identified, christened by their discoverer André Gratia in 1925 when he noticed one strain of Escherichia coli producing a toxic diffusible substance that killed a neighbouring E. coli. Since then hundreds if not thousands of peptide and protein bacteriocins have been described, which are part of the diverse arsenal of natural antibacterial compounds made by Gram-negative and Gram-positive bacteria to fend off competitors. In keeping with their being the genesis of bacteriocin research, colicins remain some of the most studied and best understood particularly in terms of how bacteriocins breach the formidable defenses of bacteria. Colicins kill cells by a variety of mechanisms that fall into two cytotoxic classes; enzymatic colicins cleave either nucleic acids or peptidoglycan precursors while pore-forming colicins depolarize the cytoplasmic membrane. Extensive biochemical, structural and biophysical work has been published for both classes. Here, we review work primarily on nuclease colicins, their cytotoxicity, immunity and import, areas that have seen some of the greatest recent advances. There is now good molecular understanding of how colicin nucleases bind their specific immunity proteins and how this has underpinned the diversification of these high affinity complexes. The key molecular recognition events in which colicins engage at the cell surface, periplasm, inner membrane and cytoplasm are also well understood. Future challenges in the field include determining how nuclease colicins translocate between these cellular compartments and how much of the translocation process is energy dependent and the extent to which the toxins must be unfolded during import. Answering these questions will not only further our understanding of the colicin entry mechanism, enhancing our ability to fully exploit the biomedical and biotechnological potential of bacteriocins, but will also provide insight into the workings of the Gram-negative cell envelope itself.
4. Capturing the Power of Van der Waals Zone in the Creation of a Novel Family of Bacteriocin-based Antibiotics
Xiao-Qing Qiu and Margaret A. Riley
The clinical potential of bacteriocins has been limited by three main concerns: (i) their narrow range of killing activity, relative to conventional antibiotics, (ii) the notion that these proteins are unlikely to reach or function at the site of most bacterial infections, and (iii) the presumed antigenicity and subsequent toxicity of protein antimicrobials. Our research on a representative of the channel-forming bacteriocins, colicin Ia, reveals that these seemingly insurmountable obstacles are, in fact, no longer relevant. Bacteriocins show no toxicity to human or animal tissues, appear not to induce an immune response by their presence and exhibit high in vivo activity in all animal tissues tested, including the circulatory system. Finally, we report here on a novel bacteriocin-modification platform that permits us to engineer the target specificity of a bacteriocin, expanding or narrowing its killing spectrum. Bacteriocins are poised to usher in a new generation in bacterial infection control.
5. The Use of Pyocins in Treating Pseudomonas aeruginosa Infections
Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen occurring in the urinary tract, skin, eye, ear, and lungs, is associated with life-threatening hospital-acquired and community-acquired infections. Although antibiotics are commonly used to fight P. aeruginosa infections, they are increasingly ineffective in the face of increasing Pseudomonas antibiotic resistance. Recent studies have focussed on the potential of pyocins, protein bacterial toxins produced by P. aeruginosa, to serve as as novel antibiotics for the treatment of P. aeruginosa infections. As with other members of bacteriocin family, pyocins mostly kill closely related species. Pyocins are currently classed into three broad categories: the S-type protease-sensitive pyocins, similar in size and mode of action to colicins of Escherichia coli, and the R and F-type protease-resistant pyocins that resemble bacteriophage tails. This chapter provides an overview of the pyocin types and their possible applications as the next generation of antimicrobials for the treatment of P. aeruginosa infections.
6. Streptococcal Bacteriocin-producing Strains as Oral Probiotic Agents
John D. F. Hale, Philip A. Wescombe, John R. Tagg and Nicholas C. K. Heng
The genus Streptococcus is one of the most diverse of the bacterial genera and presently comprises 70 defined species inhabiting a wide variety of ecological habitats. Certain species are used in the production of food products but the majority are commensal colonizers or pathogens of humans and other animals. Many are producers of bacteriocins, especially of the lantibiotic class; the tongue-dwelling Streptococcus salivarius one of the more prolific bacteriocinogenic species. Some strains of S. salivarius harbor especially large (>100 kb) megaplasmids, otherwise unreported amongst other oral bacteria. These properties, together with its extremely low pathogenic potential, favor S. salivarius as a source of oral probiotics to target infections of humans caused by other streptococci including pharyngitis (Streptococcus pyogenes) and dental caries (Streptococcus mutans). In this chapter, we provide current information on both the lantibiotic and heat-labile salivaricins produced by S. salivarius. We also present a section on the potential applications of bacteriocin-producing streptococci as oral probiotics, including a profile of S. salivarius probiotic products already available and a summary of some of the steps required to commercialize new strains.
7. Treating Bovine Mastitis with Nisin: A Model for the Use of Protein Antimicrobials in Veterinary Medicine
Sandra M. Roy, Margaret A. Riley and Joseph H. Crabb
Mastitis is the most common disease in dairy cattle, affecting approximately 56% of U.S. commercial dairy herds. Current treatments rely almost exclusively on broad-spectrum antibiotics. Resistance to these drugs is on the rise, rendering them essentially useless and requiring the development of novel approaches to both prevent and treat mastitis. This chapter reviews the current state of mastitis treatments and novel approaches that are being tested, focusing on one promising new technology produced by ImmuCell, a U.S. veterinary health company. This company has developed a bacteriocin-based strategy to combat mastitis, using the lantibiotic Nisin. This is the only bacteriocin-based product available in the U.S. and we detail its journey toward FDA approval as a New Animal Drug. This work underscores the potential to use these effective protein antimicrobials in combating disease in not only veterinary, but also human health.
8. The Phenotypic and Genotypic Landscape of Colicin Resistance
Adrienne Kicza, Christine Pureka, Diana Proctor, Margaret Riley and Robert Dorit
This study explores the landscape of emergent resistance to bacteriocins, a class of naturally occurring protein antimicrobials. Specifically, we explore the resistance mechanisms that evolve in a sensitive strain of E. coli (BZB 1011), when exposed to a panel of 10 naturally occurring colicins, the characteristic, plasmid-encoded bacteriocins of E. coli. These colicins have been selected to represent the diversity of mechanisms underlying colicin binding, translocation and killing. We first determine the frequency with which resistance to each of these colicins arises, and assess the fitness cost of the resultant resistance. We subsequently examine the pattern of cross-resistance to other colicins exhibited by these resistant strains, and use that pattern to infer the probable mechanistic basis of the selected resistance. We confirm this phenotypic inference by examining the sequence-level changes that underlie selected cases of colicin resistance. We conclude that colicin resistance is usually acquired through a limited number of readily accessible routes. These pathways likely require one (or a small number) of mutational steps; they minimize the costs and maximize the benefits of resistance. The specific pathways, in turn, depend on the environment in which selection is occurring. When the selective landscape is experimentally perturbed by the addition of an aggressive iron-chelating agent (2,2, dipyridyl) to the medium, the cost of resistance, and hence the resulting preferred paths to resistance, are altered as well. These results suggest that the landscape of resistance acquisition may consist of a relatively small number of mappable routes of escape.
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(EAN: 9781910190371 9781910190388 Subjects: [bacteriology] [bacteriology] [bacteriology] [medical microbiology] [probiotics] )