The Crisis in Antibiotic Resistance

Neu, Harold C.

doi:10.1126/science.257.5073.1064

Cited by 2,492 publications

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“…A possible explanation for the above result is that this was caused partly by different mechanisms of action in each antibiotic. Gentamicin is an aminoglycoside which causes protein synthesis inhibition by targeting to the 30S ribosomal (Neu, 1992; McManus, 1997), but levofloxacin is a quinolone antibiotic which acts by inhibiting the topoisomerase IV or DNA gyrase (Aldred et al ., 2014). Carbenicillin is a semi‐synthetic antibiotic related to penicillin (belonging to β‐lactams) which interferes with cell wall synthesis in peptidoglycan cross‐linking, and colistin (also called polymyxin E) is a polypeptide antibiotic belonging to the polymyxin group which binds to lipopolysaccharide (LPS) and phospholipids in the membrane of Gram‐negative bacteria causing cell death (Davis et al ., 1971; Evans et al ., 1999).…”

Section: Discussionmentioning

confidence: 99%

Molecular viability testing of viable but non‐culturable bacteria induced by antibiotic exposure

Lee

Bae

2017

Microbial Biotechnology

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SummaryNucleic acid amplification‐based methods are limited by their inability to discriminate between viable and dead cells. To overcome this drawback, propidium monoazide (PMA) combined with qPCR has been used to differentiate viable from nonviable cells in environmental samples. However, assessing bacterial physiology using PMA‐qPCR remains a challenge due to its incapability of detecting metabolic activities, leading to overestimation of the viable bacteria population under an inactivation condition (e.g. antibiotic treatments). A recent advanced technique to amplify ribosomal RNA precursors (pre‐rRNA) has been shown to detect viable cells because pre‐rRNAs are intermediates in rRNA synthesis. This study investigated the effect of different types of antibiotics on the bacterial viability or viable but non‐culturable (VBNC) state using both PMA‐qPCR and pre‐rRNA analyses with Pseudomonas aeruginosa. This study demonstrated that P. aeruginosa was more sensitive to colistin than it was to carbenicillin, gentamicin and levofloxacin. We could discriminate VBNC P. aeruginosa cells using PMA‐qPCR when antibiotic pressure induced the VBNC state. Also, pre‐rRNA was able to distinguish viable cells from colistin‐inactivated bacteria cells, and it could detect the presence of VBNC and persister cells. Our results showed that these two molecular methods could successfully eliminate false‐positive signals derived from antibiotics‐inactivated cells.

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Section: Discussionmentioning

confidence: 99%

Molecular viability testing of viable but non‐culturable bacteria induced by antibiotic exposure

Lee

Bae

2017

Microbial Biotechnology

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“…Beta lactamases have also been effective at protecting S. aureus against new generations and classes of antibiotics including methicillin. 2 Treatment of methicillin resistant S. aureus (MRSA) with vancomycin and increased empirical use of this antibiotic provided the antibiotic pressure associated with the emergence of vancomycin resistant enterococci and vancomycin intermediate resistant staphylococci. 3 For other pathogens, resistance took longer to emerge.…”

Section: Amr Is An Urgent Health Threat and Large Economic Problemmentioning

confidence: 99%

“…For example pneumococcal penicillin resistance was first observed only in the 1960s and subsequently spread globally due to continual changes to the antibiotic target, the bacterial penicillin binding proteins. 2 , 4 Pneumoccoci with increasing resistance to third generation cephalosporins commonly used to treat meningitis were subsequently reported to the Centers for Disease Control (CDC) in the 1990s. 5 In general, a trend is being observed that the time it takes bacteria to develop AMR after introduction of a new antibiotic is getting shorter.…”

Section: Amr Is An Urgent Health Threat and Large Economic Problemmentioning

confidence: 99%

“…46 , 47 With the often uncontrolled empirical vancomycin use particularly during elective surgeries, resistance rates could be further driven, which has already been documented by the emergence of vancomycin resistant enterococci and vancomycin-intermediate S aureus (VISA). 2 , 48 , 49 Given the disease burden and adaptability of S. aureus to develop resistance to many classes of antibiotics, the development of effective vaccines would be highly desirable in curbing disease as well as reducing AMR.…”

Section: Vaccines In Late Stage Development With Potential To Reduce Amrmentioning

confidence: 99%

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The role of vaccines in fighting antimicrobial resistance (AMR)

Jansen

Anderson

2018

Human Vaccines & Immunotherapeutics

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The problem of antimicrobial resistance (AMR) and the associated morbidity and mortality due to antibiotic resistant bacterial pathogens is not new. However, AMR has been increasing at an alarming rate with appearances of diseases caused by bacteria exhibiting resistance to not just one but multiple classes of antibiotics. The World Health Organization (WHO) supported by governments, health ministries and health agencies has formulated global action plans to combat the rise in AMR, supporting a number of proven initiatives such as antimicrobial stewardship, investments in development of new classes of antibiotics, and educational programs designed to eliminate inappropriate antibiotic use. Vaccines as tools to reduce AMR have historically been under-recognized, yet the positive effect in reducing AMR has been well established. For example Haemophilus influenzae type B (Hib) as well as Streptococcus pneumoniae (pneumococcal) conjugate vaccines have impressive track records in not only preventing life threatening diseases caused by these bacteria, but also reducing antibiotic use and AMR. This paper will describe the drivers of antibiotic use and subsequent development of AMR; it will make the case how existing vaccines are already participating in combatting AMR, describe future prospects for the role of new vaccines in development to reduce AMR, and highlight challenges associated with future vaccine development to combat AMR.

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“…Even if we are initially successful in overcoming the existing defense mechanisms of a pathogen, there are several ways by which pathogens can later overcome the initial success of a compound. Several reviews (Endicott & Ling, 1989;Neu, 1992;Walsh, 1993;Davies, 1994) have been devoted to the topic of drug resistance so that no need exists for an elaborate discussion here. It may suffice to say that multidrug resistance is becoming more and more widespread, that plasmids with resistance genes are apparently being exchanged between various species of organisms, and, quite fascinating but frightening at the same time, a certain resistance gene construct, called "conjugative transposon" (Davies, 1994), appears to have the devious property of spreading more rapidly in the microbial population in the presence than in the absence of the drug.…”

Section: Drug Resistancementioning

confidence: 99%

Protein crystallography and infectious diseases

et al. 1994

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The current rapid growth in the number of known 3-dimensional protein structures is producing a database of structures that is increasingly useful as a starting point for the development of new medically relevant molecules such as drugs, therapeutic proteins, and vaccines. This development is beautifully illustrated in the recent book, Protein structure: New approaches to disease and therapy (Perutz, 1992). There is a great and growing promise for the design of molecules for the treatment or prevention of a wide variety of diseases, an endeavor made possible by the insights derived from the structure and function of crucial proteins from pathogenic organisms and from man.We present here 2 illustrations of structure-based drug design. The first is the prospect of developing antitrypanosoma1 drugs based on crystallographic, ligand-binding, and molecular modeling studies of glycolytic glycosomal enzymes from Trypanosomatidae. These unicellular organisms are responsible for several tropical diseases, including African and American trypanosomiases, as well as various forms of leishmaniasis. Because the target enzymes are also present in the human host, this project is a pioneering study in selective design. The second illustrative case is the prospect of designing anti-cholera drugs based on detailed analysis of the structure of cholera toxin and the closely related Escherichia coli heat-labile enterotoxin. Such potential drugs can be targeted either at inhibiting the toxin's receptor binding site or at blocking the toxin's intracellular catalytic activity.Study of the Vibrio cholerae and E. coli toxins serves at the same time as an example of a general approach to structure-based vaccine design. These toxins exhibit a remarkable ability to stimulate the mucosal immune system, and early results have suggested that this property can be maintained by engineered fusion proteins based on the native toxin structure. The challenge is thus to incorporate selected epitopes from foreign pathogens into the native framework of the toxin such that crucial features of both the epitope and the toxin are maintained.That is, the modified toxin must continue to evoke a strong mucosal immune response, and this response must be directed against an epitope conformation characteristic of the original pathogen.

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The Crisis in Antibiotic Resistance

Cited by 2,492 publications

References 100 publications

Molecular viability testing of viable but non‐culturable bacteria induced by antibiotic exposure

Molecular viability testing of viable but non‐culturable bacteria induced by antibiotic exposure

The role of vaccines in fighting antimicrobial resistance (AMR)

Protein crystallography and infectious diseases

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