Antibiotics: Actions, Origins, Resistance

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The Nuts & Bolts of Antibiotics.......2004-01-21

This book was written by the eminent biochemist Christopher Walsh, whose broad research interests include the study of antibiotic action and resistance. It is extremely well written and organized, with an abundance of excellent illustrations. The approach is to give the reader an in depth but not exhausting coverage of several key topics in modern antibiotic research. Both novice and seasoned researcher will find much of value within the pages of this modest sized book. This important work is published at a period in time in which the resistance of a broad range of pathogenic bacteria to antibiotics has grown to alarming levels. At the same time, many pharmaceutical companies have recently abandoned research and development of new antibiotic agents.

Walsh starts the book with a brief chapter on fundamental antibiotic concepts. Where do antibiotics come from? How do they work? How does resistance develop? He next launches into a thorough review of the main classes of antibiotics, interweaving antibiotic chemical structures and targets of the drugs with the underlying microbial physiology processes that are targeted. He begins with the various classes of bacterial cell wall inhibitors, emphasizing the members of the large beta-lactam class, as well as glycopeptides and moenomycin. Next he delves into the multiple classes of protein synthesis inhibitors. He makes full use of the latest structural data emerging from X-ray crystallography of ribosomal subunits, to illustrate the mechanisms of drug action. He covers the macrolides, tetracyclines, and aminoglycosides, as well as the new glycylcyclines and oxazolidinones. The DNA topoisomerases are next featured as targets, and the interactions of quinolone antibiotics with DNA gyrase and topoisomerase. This chapter was a bit short and sparse in some details as compared to the preceding chapters, but does hit the main highlights. A final chapter in this section addresses other antibiotic classes such as the folate metabolism antagonists (sulfa drugs and trimethoprim), as well as peptide antibiotics.

The next section addresses the many mechanisms of antibiotic resistance. These four chapters examine different types of mechanisms employed by bacteria to evade antibiotics. Succinct coverage of the broad range of beta-lactamases and the aminoglycoside modifying (inactivating) enzymes are found in a chapter on enzymatic destruction or modification of antibiotics. This is followed by a very nice summary chapter around antibiotic efflux pumps, which again incorporates some structural biology. Unfortunately, the book was published just prior to the latest crystallographic studies of the RND class AcrB pump, which has added much to our understanding of efflux pumps. The final resistance chapter highlights target modification or replacement. The methicillin resistance story in Staphylococcus, mediated by PBP2a, is detailed, as is the resistance mediated by the mosaic PBP genes in pneumococci. Macrolide resistance by ribosomal methylation and the fascinating story of vancomycin resistance by the restructuring the terminal D-alanine dipeptide target is covered (Walsh's laboratory was a major contributor to the vancomycin story).

The next section of the book deals with the biosynthesis of antibiotics by producing organisms, primarily Streptomyces species. These chapters interweave the genetics and biochemistry of secondary metabolism. The signaling pathways used among producer organisms, as well as the gene regulation of the individual antibiotic biosynthetic genes, which are clustered on the chromosome are discussed. There is a chapter on each on polyketide antibiotic synthesis (erythromycins and tylosin) and non-ribosomal synthesis of peptide antibiotics (penicillins, bacitracin, vancomycin).

The book ends with 3 chapters on identifying new antibiotics. A survey of targets, both "old" and new is presented, and several suggestions for novel ways to interfere with bacterial function are briefly reviewed. Another chapter examines identifying new chemical entities with antibacterial properties. The initial part of the chapter emphasizes combinatorial chemistry approaches. Unfortunately, this process to date has led to only sparse results, with some inhibitors identified. As Walsh notes, the conversion of a chemical inhibitor of an antibacterial enzyme target to a lead compound that can be subsequently endowed with all the myriad pharmacological properties necessary to be a drug is an extremely daunting task. The vast majority of compounds identified cannot be successfully modified to possess the properties necessary to be a drug. A second approach that he covers, the modification by genetic means of antibiotic producing organisms to synthesize new antibiotics (combinatorial biosynthesis), may be more promising.

Book Description

This reference summarizes the latest research on the structure, function, and design of synthetic and natural peptide antibiotics, describing practical applications of these compounds in food preservation and packaging, and in the prevention and treatment of infectious diseases by direct anti-bacterial action and as part of the adaptive immune response. Peptide Antibiotics discusses these unique compounds and their many and exciting applications, including: · the distribution and classification of diverse antimicrobial peptides throughout nature · the role in host defense of mucosal surface peptide antibiotics such as defensins and cathepsins · the biosynthesis of lanthionine-containing antibiotics including nisin, epidermin, and mersacidin · the genetic basis determining the production of bacterial peptide antibiotics · the potential commercial use of magainin, nisin, and lacticin peptides as anti-infective agents · the use of nisin as a commercial food preservative With contributions from 19 world-renowned experts in the field, Peptide Antibiotics is an indispensable source of information for pharmaceutical scientists, medicinal and organic chemists and biochemists, microbiologists, infectious disease specialists, molecular biologists, and upper-level undergraduate and graduate students in these disciplines.

Selected Exercises for Microbes in Action, Fourth Edition

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Selected Exercises for Microbes in Action, Fourth Edition
Harry W. Seeley , Paul J. Vandemark , and John J. Lee
Manufacturer: W. H. Freeman
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Binding: Paperback

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ASIN: 0716721112

Microbes in Action: A Laboratory Manual of Microbiology

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Microbes in Action: A Laboratory Manual of Microbiology
Harry W. Seeley , Paul J. Vandemark , and John J. Lee
Manufacturer: W. H. Freeman
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Binding: Paperback

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ASIN: 0716721007

Elements of Pharmacology: A Primer on Drug Action

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Elements of Pharmacology: A Primer on Drug Action
Peter J. Bentley
Manufacturer: Cambridge University Press
ProductGroup: Book
Binding: Hardcover

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Book Description

Written primarily for students of medicine, pharmacy, and pharmacology, this introductory book provides a concise summary of the principles that underlie the science of pharmacology. It presents the basic concepts required for understanding the use, mechanisms of action, toxicity and side effects, and therapeutic application of drugs in man. Thus the book may also be of interest to medical practitioners and to biological and medical scientists. Among topics covered are the sources of drugs, the way they are administered and dealt with in the body, as well as concepts about the nature of their actions. The last include their chemical interactions with components of cells and the manner in which these lead to therapeutically desirable as well as undesirable and even toxic effects. In addition, clinically related subjects, such as drug interactions, teratogenic and carcinogenic effects are discussed. The development and testing of new drugs are also described. For easy reference, at the back of the book there is a glossary of drugs named in the text.

ANTIMICROBIAL DRUG ACTION (Medical Perspectives)

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ANTIMICROBIAL DRUG ACTION (Medical Perspectives)
Dr Pete Lambert
Manufacturer: Garland Science
ProductGroup: Book
Binding: Paperback

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Biochemistry and Molecular Biology of Antimicrobial Drug Action

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Review from The Journal of Medical Microbiology, 50:3 (2201)

Biochemistry and Molecular Biology of Antimicrobial Drug Action
Trevor J. Franklin , and G.A. Snow
Manufacturer: Springer
ProductGroup: Book
Binding: Hardcover

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ASIN: 0387225544

Book Description

This stimulating new edition of the well-respected title Biochemistry and Molecular Biology of Antimicrobial Drug Action primarily covers medically important antimicrobial agents, but also includes some compounds not in current medical use, which have been invaluable as research tools in biochemistry.

Since the previous edition of this book, the impact of molecular biology on our understanding of the mechanisms of antimicrobial action and drug resistance has evolved significantly. This is reflected in the book’s coverage, with new material dealing with the remarkable recent developments in unraveling the complex molecular details of drug interactions with such key targets as ribosomes and the enzymes of nucleic acid replication and microbial cell wall biosynthesis. The new addition also reviews key advances in the biochemistry and molecular biology of drug-resistant pathogens including viruses, parasitic protozoa, fungi, and the much feared ‘superbugs’ such as MRSA.

Completely updated and rewritten, Biochemistry and Molecular Biology of Antimicrobial Drug Action will be of great use to medical and biological sciences students taking courses in pharmacology, molecular biology, microbiology, biochemistry and chemotherapeutics. Because of the wealth of information within the covers of this important book, all those involved in research into drug action and development, whether in the pharmaceutical industry or academia, will find Biochemistry and Molecular Biology of Antimicrobial Drug Action invaluable. It should also be on the shelves of all libraries, in university medical schools and departments of biological sciences, biochemistry, and pharmacology.

Customer Reviews:

Review from The Journal of Medical Microbiology, 50:3 (2201).......2002-07-02

"...an authorative, lucid, and well-produced account of the action of antimicrobial compounds. The fifthedition represents a thorough revision of the whole text and it is highly recommended to all those involved in developing, testing and using these important agents."

Clinical Applications of the Interferons

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Clinical Applications of the Interferons

Manufacturer: A Hodder Arnold Publication
ProductGroup: Book
Binding: Hardcover

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Book Description

This comprehensive, up-to-date summary of current knowledge covers the biological structure and function, and the clinical applications, of the interferons. The history of the development and introduction of the interferons into clinical practice are discussed, followed by a thorough exploration of their mechanisms of action and possible future developments in the field. Sections on the use of interferons in the treatment of solid tumors and viral, hematological and non-malignant disease emphasise the multidisciplinary nature of the field. Toxicities associated with therapy are also covered. Thus 'Clinical Applications of the Interferons' is an essential reference for trainee and practising virologists, immunologists, hematologists, oncologists and other specialists with an interest in this rapidly expanding area.

Coumarins: Biology, Applications, and Mode of Action

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Coumarins: Biology, Applications, and Mode of Action

Manufacturer: Wiley
ProductGroup: Book
Binding: Hardcover

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ASIN: 0471969974

Book Description

Coumarins: Biology, Applications and Mode of Action predominantly focuses on the parent compound, coumarin, and its main metabolite in humans, 7-hydroxycoumarin. It describes in detail every facet of these compounds including history, toxicology, chemistry, metabolism, analysis, clinical, veterinary and other applications, their roles as immunomodulatory agents and speculates on their mode of action.

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A short course in qualitative chemical analysis
John Howard Appleton
Manufacturer: Silver, Burdett & Co
ProductGroup: Book
Binding: Unknown Binding

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ASIN: B00087I6KG

Book Description

This volume presents the proceedings of the Seventh International Colloquium on Finite or Infinite Dimensional Complex Analysis held in Fukuoka, Japan. The contributions offer multiple perspectives and numerous research examples on complex variables, Clifford algebra variables, hyperfunctions and numerical analysis.

Finite or Infinite Dimensional Complex Analysis and Applications (Advances in Complex Analysis and Its Applications)

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Finite or Infinite Dimensional Complex Analysis and Applications (Advances in Complex Analysis and Its Applications)

Manufacturer: Springer
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Binding: Hardcover

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ASIN: 1402076584

Book Description

There is almost no field in mathematics that does not use mathematical analysis. Computer methods in applied mathematics are often based on statements and procedures of mathematical analysis as well. An important part of mathematical analysis is complex analysis because it has many applications in various branches of math.
Present trends in complex analysis, which are reflected in the book, are mainly concentrated on the following four research directions:

-Value distribution theory and its applications,
-Holomorphic functions in several (finitely or infinitely many) complex variables,
-Clifford analysis, I.e., complex methods in higher-dimensional real Euclidian spaces,
-Generalized analytic functions.

A specific feature of today's complex analysis is combining methods of Clifford analysis. This leads to a theory of multi-regular functions.

Finite or Infinite Dimensional Complex Analysis (Lecture Notes in Pure and Applied Mathematics)

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Finite or Infinite Dimensional Complex Analysis (Lecture Notes in Pure and Applied Mathematics)
Joji Kajiwara
Manufacturer: NY
ProductGroup: Book
Binding: Paperback
ASIN: B000MUEF2W

Finite or Infinite Dimensional Complex Analysis and Applications

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Finite or Infinite Dimensional Complex Analysis and Applications
Le Hung Son
Manufacturer: Springer-Verlag New York, LLC
ProductGroup: Book
Binding: Hardcover
ASIN: B000MUXC3K

Book Description

A year’s worth of the most powerful, the most startling, the smartest and most astute…

“Ciudad de la Muerte” by Cecilia Balli, from Texas Monthly
“Code of Dishonor” by Clara Bingham, from Vanity Fair
“Lord of the Drug Ring” by Charles Bowden, from GQ
“The Dark Art of Interrogation” by Mark Bowden, from The Atlantic Monthly
“Possessed” by Luke Dittrich, from Atlanta magazine
“Night of the Bullies” by Robert Draper, from GQ
“Stephanie” by James Ellroy, from GQ
“Who Is the Boy in the Box?” by Sabrina Rubin Erdely, from Philadelphia magazine
“Who Shot Mohammed al-Dura?” by James Fallows, from The Atlantic Monthly
“The Professor and the Porn” by Elisabeth Franck, from New York magazine
“The Old Man and the Gun” by David Grann, from The New Yorker
“CSC: Crime Scene Cleanup” by Pat Jordan, from Playboy
“A Miscarriage of Justice” by Robert F. Kennedy Jr., from The Atlantic Monthly
“Watching the Detectives” by Jay Kirk, from Harper’s Magazine
“For the Love of God” by Jon Krakauer, from GQ
“Chief Bratton Takes on LA” by Heather Mac Donald, from City Journal
“Not Guilty by Reason of Afghanistan” by John H. Richardson, from Esquire
“Megan’s Law and Me” by Brendan Riley, from Details
“Unfortunate Con” by Mark Schone, from The Oxford American
“To Kill or Not to Kill” by Scott Turow, from The New Yorker

Customer Reviews:

Delivers as Promised.......2005-09-30

As the title says, enclosed in the pages of this book is the best American Crime Writing of the year. The stories cover a wide range of criminals, their crimes and the individuals victimized. By including different authors, the styles of each contrast nicely as each weaves his or her own tale. Each story and storyteller is unique. I have read the 2002 and the 2003 edition and this book lives up to its predecessors' lofty standards.

"Writing So Good, It's Almost Criminal...".......2004-10-31

Best American Crime Writing: 2004 Edition, $14.00 US, is an anthology of twenty crime stories gathered by Otto Penzler and Thomas H. Cook. These yarns were originally published in magazines -- such as Atlanta, Details, GQ, and The New Yorker -- that were sold in 2003. Some are similar in topic, but each story is extremely unique as told from the vantage point of its author. Some big name writers happened to appear in this issue, such as James Ellroy, Jon Krakauer, and Scott Turow, but I prefer the original tack of "lesser known authors" that the Editors pursued in previous issues. This edition also includes an introduction by Joseph Wambaugh, whom discusses the need for tort reform to protect crime writers from frivolous lawsuits in a concise six page case -- but it seems that with these buzz words, he's really trying to score points with politicians in this, an election year.

My favorite story in this collection is "Ciudad de la Muerte," a feature that first appeared in Texas Monthly, and that was written by Cecilia Balli. "Ciudad de la Muerte," is both chilling and riveting -- a story of the disappearance of more than three hundred women from Juarez, Mexico, over the last eleven years. But more specifically -- it narrows in on an incident whereby eight bodies were found in canals and irrigation ditches of a cotton field in 2001, and the aftermath of that specific grisly discovery. It's a particularly strong piece, because the writer examines her own fears as she explores the city of Juarez, the shady justice system of Mexico, and the final fate of these women. I'm curious about one thing though, and it's not really clear from the writing, or at least to me. One of the girls that disappeared in that November was named Esmerelda Monnreal, and on page 18 the storyteller reveals that Esmerelda had an older sister named Cecilia also, that had moved to Colorado with her husband. Is this in fact the same Cecilia that authored the story? Or is she simply sympathizing with the victim, because of coincidental names? I could use some clarification on that question. Based on the quality of her work, I'm very eager to read the finished book that Balli is deriving from this piece. This story may also spur you to do further reading on the subject, and spur you to support political action on the matter. Try Googling "Juarez" AND "Disappeared," and reading everything. You may want to write a letter to your Representative or Senator, after perusing these pages, to exhort them to involve the FBI in an investigation of these murders, which should not be allowed to go unsolved, because these women certainly deserve some kind of Justice.

My second "most liked" parable of the group is "Who Is The Boy In The Box?," a twenty-four page recounting of a forty-six year old mystery, penned by Sabrina Rubin Erdely, that first appeared in Philadelphia magazine. And it's a sad story. It's about a little boy that was found in a cardboard box, in a dump, off a path, beaten and dead in Northeast Philly's Fox Chase neighborhood. It's also about the man who ended up performing the fingerprinting and footprinting at the morgue that day, Bill Kelly. The case never left the young policeman's mind. He was 29 at the time the child was found, and consequently developed a lifelong dedication to the case. His most fervent wish was to simply give the boy a name, because somebody must have loved the boy at some point, right? He couldn't imagine anyone harming a child like that, or that the child would be buried in a potter's field, no name on the stone. Police were baffled by "the boy in the box," because every lead fizzled. Other people took interest too -- Remington Bristow, an ME's investigator. The Vidocq Society, a detective, Sam Weinstein. Someone in another Medical Examiner's office, Joe McGillen. In 1998, after the boy was exhumed for modern DNA testing, he was reburied in Ivy Hill Cemetery, in Mt. Airy, PA. The case was featured on America's Most Wanted in 1999, spawning dozens of leads. Someone then came forward with knowledge of the murder, and the facts checked out, and the story is plausible, although the woman did suffer from some psychiatric problems, and some minor lingering doubt remains. She said her mother killed the boy, the boy was purchased as an infant, that he was raised in their basement, and he was mute when he died. Bill Kelly had taken to calling the child Sean over the years, a good Irish name. But the woman that had finally come forward in 2000 gave Bill one small thing. In November of 2003, as he turned to leave from the grave, Bill touched the headstone and said "Good-bye, Jonathan, I'll see you again soon..."

And I suppose my third favorite gem from this volume would be "Stephanie," a chronicle of the unsolved 1965 murder of Stephanie Lynn Gorman, a Los Angeles schoolgirl, as told by James Ellroy, that first appeared in GQ magazine. It's fair to say that Ellroy, who has a gift for writing about the past, is infatuated with his subject here -- and that his writing is eloquent and rhapsodic as usual. Ellroy didn't know the girl, but he's just slightly older, by a year, and he lived within five miles of the girl. The story starts while he's reviewing the murder book. Crime scene: a corner house, Hillsboro and Sawyer, West L.A.

Detective Bureau/Homicide Division/LAPD
DR#65-538-991 [Murder/187 PC]
Victim: Stephanie Lynn Gorman/White Female/Age 16
DOB: 06-11-1949 - DOD: 08-05-1965

Ellroy clinically eyes the crime scene, breaks down the timeline, develops the suspects, pencils in the detectives, chases some leads. Dragnet type stuff. They sprint through 5,000 names. They turns up 201 rap sheets. They arrest a few possibilities -- but they're sprung. Of course he isn't really there, he's just imagining that he's there. A reconstruction. Powerful stuff. Ellroy's friend Rick Jackson tells him about Stephanie, late of Hamilton High. He's LAPD Homicide. It's the year 2000. Stephanie's sister attends a party. She's fiftyish, requests an update. Rick makes calls, Detective Dave Lambkin picks it up, sends unknown prints from the 1965 crime scene to the modern FBI, gets a print match. I'll leave the rest to you. Interestingly enough, you can still map some of the locations mentioned in the story "Stephanie" on MS Streets & Trips.

For the purpose of this review, and in favor of leaving you some stories to discover on your own, I've decided to summarize only three of these non-fiction tales. Almost all of the other items in this anthology, such as A Miscarriage Of Justice, For The Love Of God, Not Guilty By Reason Of Afghanistan and Unfortunate Con are just as good, in terms of quality. There was only one story that I skimmed, and one that I couldn't bring myself to finish. I read the remaining eighteen, sometimes more than once. The trio of story lines I've decided to outline for you here are simply the most interesting in my opinion. Penzler and Cook did a fairly good job of selecting stories, but I really would like to see them select from a much greater pool of sources. I think the ideal mix would be three fifths magazine stories, two fifths long-form newspaper articles. And perhaps they should also consider including pieces that were published exclusively on the Internet. Currently they only survey magazine articles, which seems unfair, since so many newspapers also provide excellent crime writing. And having four stories in this issue from GQ? That seems like over representation to me. Ditto having some of the same authors appearing year after year, please, no Robert Draper in 2005. There are many great writers of crime fiction, so the Editors should really give more scribes a chance. And one last note for Base Art Co. who designed the back cover -- white on yellow was a horrid idea -- the story titles on the reverse were nearly illegible.

And If you, my constant reader, seek out Best American Crime Writing: 2004 Edition based on the recommendation here, you'll probably also want to pick up Best American Crime Writing: 2003 Edition and Best American Crime Writing from 2002, the first in this series. Or you may also want to pursue six of the books I've hyperlinked below, which are by the authors that Cook. and Penzler chose to feature in this edition. If you'd like to send stories for possible inclusion in this series, submissions should be directed to Otto Penzler, c/o The Mysterious Bookshop, 129 West 56th Street, New York, NY 10019.

If any of the great authors that have contributed to this series happen to read this, may I please encourage you to write a story about Victoria Snelgrove, entitled "Non-Lethal Weapons?"

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