Permeability Barriers Of The Bacterial Cell

Structure of Bacterial Cell Envelopes The envelope of the bacterial cell consists of all structures external to the cytoplasm, including the cytoplasmic membrane (CM), which immediately overlies the cytoplasm the cell wall, composed largely of the polymer peptidoglycan (cross linked to various degrees in different species) and, in Gram-negative bacteria, the outer membrane (OM). Gram-positive bacteria lack an OM, but have in general a much thicker cell wall layer than do Gram-negatives. In...

Staphylococcus Aureus

In S. aureus, resistance to methicillin (and thereby by definition all P-lactam antibiotics) is dependent on the presence of the mecA gene, which encodes PBP2a, an alternative penicillin-binding protein that despite its name does not bind P-lactam antibiotics and is therefore insensitive to their action. However, not only S. aureus may harbor the mecA gene. It is also found among coagulase-negative staphylococci (CoNS), including S. epidermidis, which is normally a human commensal. Therefore,...

Evolution Of Antibiotic Resistance

P-Lactam Resistance and Clinical Consequences Since its detection in 1967, penicillin resistance in S. pneumoniae has become increasingly prevalent worldwide 16 . A S. pneumoniae isolate is considered to lack susceptibility when the minimal inhibitory concentration (MIC) of penicillin is greater than 0.06 mg L 17 and is treated as a PNSP. Isolates for which penicillin MICs ranged from 0.12 to 1 mg L fit the category of intermediate susceptibility and high-level resistance to penicillin, when...

Modification Of Uptake By Administration Of A Second Agent

Combined antibiotic therapy has of course a venerable history in infectious disease therapy. However, increased understanding of bacterial physiology and structure can provide possibilities for therapeutic use of agents that are not themselves antimicrobial, but have an enhancing effect on the action of a known antibiotic. For example, Rajyaguru and Muszynski 45 showed that susceptibility of B. cepacia isolates to several standard antibiotics could be significantly enhanced in vitro (four-fold...

Resistance Associated With Speciesspecific Variations And Mutational Alteration In Envelope Structure

Specificity of porins for substrates is sometimes extended to antibiotics for example, the P-lactam imipenem is specifically taken up by Pseudomonas aeruginosa through the substrate-specific porin OprD 14 . OprD formation is highly regulated by nitrogen and carbon sources 15 , and its down-regulation results in imipenem resistance 16 , as do mutations in OprD 17 . Do altered porins occur in drug-resistant clinical isolates In some species, the answer would seem to be yes Mallea et al. 18...

Antiinfective Drug Discovery And Efflux Pump Inhibitors

Approaches to combating drug efflux offer new opportunities to combat antibiotic resistance development across the spectrum of drugs in development and in clinical use. The first category includes antibiotics approved by the FDA from 1998 to 2005, including rifapentine, quinupristin dalfoprystin, moxifloxacin, gatifloxacin, linezolid, ceftidoren, ertapenem, gemifloxacin, daptomycin, telithromycin, and tigecycline 59,60 . The second category are antibiotics currently in clinical trials, such as...

Microbial Drug Resistance A Historical Perspective

Drug-Fastness Disinfection Microbial Metabolism and Adaptation Adaptation or Mutation Drug Dependence Multiple Drug Resistance and Cross Resistance Newly Found Modes of Resistance References Almost as soon as it was known that microorganisms could be killed by certain substances, it was recognized that some microbes could survive normally lethal doses and were described as drug-fast (German -fest -proof, as in feuerfest fire-proof hence drug-proof, in common usage by at least 1913). These early...

Global Regulators Of Antibiotic Resistance In Escherichia Coli

Undoubtedly, the best-characterized global antibiotic resistance regulatory system is the mar (multiple antibiotic resistance) system in E. coli. An excellent review of the molecular genetics of this system has been published 1 . Much of the detailed work described in that review is only summarized here, and the reader is encouraged to look to that source for additional detailed information. The mar locus was first described in 1983 in the pioneering studies of George and Levy. As a component...

MDRs In Clinically Relevant Drug Resistance

Five families of bacterial drug efflux pumps have been identified to date 1 . However, it is mostly members of a single resistance nodulation division super family (RND) found in Gram-negative species that are implicated in clinically relevant resistance. In this section, we will review the structure and mechanism of RND MDRs. Efflux is most effective when working in cooperation with other resistance mechanisms. Reduced uptake across the outer membrane of Gram-negative bacteria, which is a...

Target Modification And Protection Due To Acquired Genes And Proteins

Macrolide, Streptogramin, and Lincosamide Resistance Macrolides, streptogramins, and lincosamides inhibit bacterial protein synthesis by binding to the 23S rRNA component of the bacterial 50S ribosomal subunit 90 . One of the most common mechanisms of resistance to these three classes of antimicrobials involves posttranscriptional alteration of a specific base of rRNA that results in ribosomes with reduced drug affinity 51 . Specifically, methylation of an adenine at position 2058 of 23S rRNA...

Epidemiology Of S Pneumoniae

Population Structure of S. pneumoniae Asymptomatic carriage of pneumococci in the throat or nasopharynx is widespread, with carriage rates being especially high in children 91-93 . There is also clear evidence of spread among families 94 , and colonization by multiple pneumococcal capsular types has also been reported 91 . Some serotypes are particularly associated with disease in children 95 or adults 96 ) and others with carriage 97 or HIV infection 98 . However, it is only just becoming...

Phenotyping Versus Genotyping

The correct detection of antibiotic resistance of clinical isolates is of great importance for optimal antibiotic therapy and successful treatment of patients. This only becomes more important with increasing prevalence of antibiotic-resistant isolates. Testing is not only required for therapy, but also to monitor the spread of antibiotic-resistant organisms or resistance genes through the hospital, community, or other reservoirs, such as animal husbandry. Before the advent of molecular...

Charting The Movement Of Resistance Genes Into Bacteroides

Given that the ermB and ermG genes had been found previously exclusively in the Gram-positive bacteria, is it possible that these genes were obtained from Grampositive bacteria Recently, it became possible to ask this question, because a CTn that carries ermB, CTnBST, was found in Bacteroides spp It has been sequenced. The results of this analysis are both revealing and confusing 43 . We had hoped that the answer would be a simple one, that is, that a single CTn of Gram-positive origin would be...

Contents

Preface About the Editors Chapter 1 Microbial Drug Resistance A Historical Perspective 1 Chapter 2 Ecology of Antibiotic Resistance Genes 11 Abigail A. Salyers, Nadja Shoemaker, and David Schlesinger Chapter 3 Global Response Systems That Confer Resistance 23 Chapter 4 Multidrug Efflux Pumps Structure, Mechanism, Olga Lomovskaya, Helen I. Zgurskaya, Keith A. Bostian, and Kim Lewis Chapter 5 Mechanisms of Aminoglycoside Antibiotic Resistance 71 Chapter 6 Resistance to P-Lactam Antibiotics...

About the Editors

Wax, Ph.D., was an Associate Research Fellow at Pfizer Global Research until his retirement in 2005. He received his B.S. in Chemical Engineering from the Polytechnic University of New York and his M.S. in Biophysics from Yale University. He followed his mentor, Professor Ernest Pollard, to The Pennsylvania State University, University Park, where he received his Ph.D. in Biophysics. He was a Staff Fellow at the U.S. National Institutes of Health (NIH), Bethesda, Maryland, and an NIH...