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1.
J Enzyme Inhib Med Chem ; 39(1): 2318830, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38488135

ABSTRACT

The urgent demand for effective countermeasures against metallo-ß-lactamases (MBLs) necessitates development of novel metallo-ß-lactamase inhibitors (MBLIs). This study is dedicated to identifying critical chemical moieties within previously developed MBLIs, and critical MBLs should serve as the target in MBLI evaluations. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic literature analysis was conducted, and the NCBI RefSeq genome database was exploited to access the abundance profile and taxonomic distribution of MBLs and their variant types. Through the implementation of two distinct systematic approaches, we elucidated critical chemical moieties of MBLIs, providing pivotal information for rational drug design. We also prioritised MBLs and their variant types, highlighting the imperative need for comprehensive testing to ensure the potency and efficacy of the newly developed MBLIs. This approach contributes valuable information to advance the field of antimicrobial drug discovery.


Subject(s)
beta-Lactamase Inhibitors , beta-Lactamases , beta-Lactamase Inhibitors/pharmacology , Anti-Bacterial Agents/pharmacology , Drug Design
2.
Int J Mol Sci ; 24(20)2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37894890

ABSTRACT

Pseudomonas aeruginosa is the primary opportunistic human pathogen responsible for a range of acute and chronic infections; it poses a significant threat to immunocompromised patients and is the leading cause of morbidity and mortality for nosocomial infections. Its high resistance to a diverse array of antimicrobial agents presents an urgent health concern. Among the mechanisms contributing to resistance in P. aeruginosa, the horizontal acquisition of antibiotic resistance genes (ARGs) via mobile genetic elements (MGEs) has gained recognition as a substantial concern in clinical settings, thus indicating that a comprehensive understanding of ARG dissemination within the species is strongly required for surveillance. Here, two approaches, including a systematic literature analysis and a genome database survey, were employed to gain insights into ARG dissemination. The genome database enabled scrutinizing of all the available sequence information and various attributes of P. aeruginosa isolates, thus providing an extensive understanding of ARG dissemination within the species. By integrating both approaches, with a primary focus on the genome database survey, mobile ARGs that were linked or correlated with MGEs, important sequence types (STs) carrying diverse ARGs, and MGEs responsible for ARG dissemination were identified as critical factors requiring strict surveillance. Although human isolates play a primary role in dissemination, the importance of animal and environmental isolates has also been suggested. In this study, 25 critical mobile ARGs, 45 critical STs, and associated MGEs involved in ARG dissemination within the species, are suggested as critical factors. Surveillance and management of these prioritized factors across the One Health sectors are essential to mitigate the emergence of multidrug-resistant (MDR) and extensively resistant (XDR) P. aeruginosa in clinical settings.


Subject(s)
Anti-Bacterial Agents , Pseudomonas aeruginosa , Animals , Humans , Drug Resistance, Microbial/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
3.
Tuberculosis (Edinb) ; 138: 102298, 2023 01.
Article in English | MEDLINE | ID: mdl-36580851

ABSTRACT

Ecumicin and rufomycin 4-7 disrupt protein homeostasis in Mycobacterium tuberculosis by inhibiting the proteolytic activity of the ClpC1/ClpP1/ClpP2 complex. Although these compounds target ClpC1, their effects on the ATPase activity of ClpC1 and proteolytic activity of ClpC1/ClpP1/ClpP2 vary. Herein, we explored the ClpC1 molecular dynamics with these compounds through fluorescence correlation spectroscopy. The effect of these compounds on the ATPase activity of ClpC1-cys, the recombinant protein for fluorescence labeling, and proteolytic activity of ClpC1-cys/ClpP1/ClpP2 were identical to those of native ClpC1, whereas the intermolecular dynamics of fluorescence-labelled ClpC1 were different. Treatment with up to 1 nM ecumicin increased the population of slower diffused ClpC1 components compared with ClpC1 without ecumicin. However, this population was considerably reduced when treated with 10 nM ecumicin. Rufomycin 4-7 treatment resulted in a slower diffused component of ClpC1, and the portion of this component increased in a concentration-dependent manner. Ecumicin can generate an abnormal ClpC1 component, which cannot form normal ClpC1/ClpP1/ClpP2, via two different modes. Rufomycin 4-7 only generates slower diffused ClpC1 component that is inadequate to form normal ClpC1/ClpP1/ClpP2. Overall, we demonstrate that ecumicin and rufomycin 4-7 use different action mechanisms to generate abnormal ClpC1 components that cannot couple with ClpP1/ClpP2.


Subject(s)
Mycobacterium tuberculosis , Mycobacterium tuberculosis/genetics , Bacterial Proteins/metabolism , Adenosine Triphosphatases/metabolism , Adenosine Triphosphatases/pharmacology
6.
Front Bioeng Biotechnol ; 8: 574010, 2020.
Article in English | MEDLINE | ID: mdl-33195136

ABSTRACT

Hutchinson-Gilford progeria syndrome (HGPS) is a rare, fatal, and genetic disorder in the LMNA gene encoding for prelamin A. Normally, prelamin A is processed to become lamin A protein. In HGPS patients, there is a heterozygous mutation in LMNA gene, in which there is a deletion of genetic codes responsible for 50 amino acids at the C-terminus of prelamin A. The processing of the abnormal prelamin A results in abnormal lamin A protein, called progerin, causing symptoms of accelerated early aging, probably due to the inflammaging process. It is well known that adipose tissue-derived mesenchymal stem cells (MSCs) have anti-inflammatory effects by modulating inflammatory cytokines and by extracellular vesicles. Here, we present a case of an HGPS patient who responded positively to injections of allogeneic haploidentical adipose tissue-derived stromal vascular fractions containing MSCs by showing rapid height and weight growth along with increased blood level of insulin-like growth factor 1.

7.
J Vis Exp ; (139)2018 09 29.
Article in English | MEDLINE | ID: mdl-30320755

ABSTRACT

Osteoarthritis (OA) is one of the most common debilitating disorders. Recently, numerous attempts have been made to improve the functions of the knees by using different forms of mesenchymal stem cells (MSCs). In Korea, bone marrow concentrates and cord blood-derived stem cells have been approved by the Korean Food and Drug Administration (KFDA) for cartilage regeneration. In addition, an adipose tissue-derived stromal vascular fraction (SVF) has been allowed by the KFDA for joint injections in human patients. Autologous adipose tissue-derived SVF contains extracellular matrix (ECM) in addition to mesenchymal stem cells. ECM excretes various cytokines that, along with hyaluronic acid (HA) and platelet-rich plasma (PRP) activated by calcium chloride, may help MSCs to regenerate cartilage and improve knee functions. In this article, we presented a protocol to improve knee functions by regenerating cartilage-like tissue in human patients with OA. The result of the protocol was first reported in 2011 followed by a few additional publications. The protocol involves liposuction to obtain autologous lipoaspirates that are mixed with collagenase. This lipoaspirates-collagenase mixture is then cut and homogenized to remove large fibrous tissue that may clog up the needle during the injection. Afterwards, the mixture is incubated to obtain adipose tissue-derived SVF. The resulting adipose tissue-derived SVF, containing both adipose tissue-derived MSCs and remnants of ECM, is injected into knees of patients, combined with HA and calcium chloride activated PRP. Included are three cases of patients who were treated with our protocol resulting in improvement of knee pain, swelling, and range of motion along with MRI evidence of hyaline cartilage-like tissue.


Subject(s)
Adipose Tissue/growth & development , Cartilage/growth & development , Mesenchymal Stem Cells/metabolism , Osteoarthritis/therapy , Regeneration/physiology , Humans , Osteoarthritis/pathology
8.
Int J Mol Sci ; 19(7)2018 Jul 23.
Article in English | MEDLINE | ID: mdl-30041472

ABSTRACT

Adipose tissue-derived stem cells (ASCs) in the form of stromal vascular fraction (SVF) and cultured expansion have been applied in clinical settings in some countries to treat osteoarthritis (OA) of knees, one of the most common debilitating, incurable disorders. Since the first report of successful cartilage-like tissue regeneration with autologous adipose SVF containing ASCs, there has been a gradual increase in the number of publications confirming such results. Thus far, most of the reports have been limited to treatments of OA of knees. Recently, successful applications of adipose SVF in treating OA of ankles and hips have been reported. In addition, several groups have reported modified methods of applying adipose SVF, such as combining bone marrow stimulation with adipose SVF or adding additional extracellular matrix (ECM) in treating OA. Here, we present an updated, systematic review of clinical effectiveness and safety in treating OA of knees, ankles, and one hip since 2016 using ASCs in the form of adipose SVF or in cultured expansion, along with a description and suggestion of potential biological mechanisms of cartilage regeneration.


Subject(s)
Cartilage/physiology , Mesenchymal Stem Cell Transplantation/methods , Osteoarthritis/therapy , Regeneration , Adipose Tissue/cytology , Cartilage/cytology , Chondrogenesis , Humans
9.
J Microbiol Biotechnol ; 28(2): 284-292, 2018 Feb 28.
Article in English | MEDLINE | ID: mdl-29169221

ABSTRACT

A novel ß-agarase, AgaJ5, was identified from an agar-degrading marine bacterium, Gayadomonas joobiniege G7. It belongs to the glycoside hydrolase family 86 and is composed of 805 amino acids with a 30-amino-acid signal peptide. Zymogram analysis showed that purified AgaJ5 has agarase activity. The optimum temperature and pH for AgaJ5 activity were determined to be 30°C and 4.5, respectively. AgaJ5 was an acidic ß-agarase that had strong activity at a narrow pH range of 4.5-5.5, and was a cold-adapted enzyme, retaining 40% of enzymatic activity at 10°C. AgaJ5 required monovalent ions such as Na+ and K+ for its maximum activity, but its activity was severely inhibited by several metal ions. The Km and Vmax of AgaJ5 for agarose were 8.9 mg/ml and 188.6 U/mg, respectively. Notably, thin-layer chromatography, mass spectrometry, and agarose-liquefication analyses revealed that AgaJ5 was an endo-type ß-agarase producing neoagarohexaose as the final main product of agarose hydrolysis. Therefore, these results suggest that AgaJ5 from G. joobiniege G7 is a novel endo-type neoagarohexaose-producing ß-agarase having specific biochemical features that may be useful for industrial applications.


Subject(s)
Agar/metabolism , Alteromonadaceae/enzymology , Alteromonadaceae/metabolism , Glycoside Hydrolases/chemistry , Glycoside Hydrolases/metabolism , Alteromonadaceae/genetics , Amino Acid Sequence , Bacterial Proteins/biosynthesis , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Cloning, Molecular , Cold Temperature , Enzyme Activation , Enzyme Assays , Escherichia coli , Gene Expression Regulation, Bacterial , Hydrogen-Ion Concentration , Kinetics , Metals/antagonists & inhibitors , Protein Sorting Signals , Temperature , Viscosity
10.
Article in English | MEDLINE | ID: mdl-29209595

ABSTRACT

Klebsiella pneumoniae is one of the most clinically relevant species in immunocompromised individuals responsible for community-acquired and nosocomial infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Since the mid-1980s, hypervirulent K. pneumoniae, generally associated with the hypermucoviscosity phenotype, has emerged as a clinically significant pathogen responsible for serious disseminated infections, such as pyogenic liver abscesses, osteomyelitis, and endophthalmitis, in a generally younger and healthier population. Hypervirulent K. pneumoniae infections were primarily found in East Asia and now are increasingly being reported worldwide. Although most hypervirulent K. pneumoniae isolates are antibiotic-susceptible, some isolates with combined virulence and resistance, such as the carbapenem-resistant hypervirulent K. pneumoniae isolates, are increasingly being detected. The combination of multidrug resistance and enhanced virulence has the potential to cause the next clinical crisis. To better understand the basic biology of hypervirulent K. pneumoniae, this review will provide a summarization and discussion focused on epidemiology, hypervirulence-associated factors, and antibiotic resistance mechanisms of such hypervirulent strains. Epidemiological analysis of recent clinical isolates in China warns the global dissemination of hypervirulent K. pneumoniae strains with extensive antibiotic resistance in the near future. Therefore, an immediate response to recognize the global dissemination of this hypervirulent strain with resistance determinants is an urgent priority.


Subject(s)
Drug Resistance, Bacterial/genetics , Drug Resistance, Bacterial/physiology , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/pathogenicity , Virulence Factors/genetics , Bacteremia/epidemiology , Bacteremia/microbiology , Bacterial Capsules/classification , Bacterial Capsules/genetics , Bacterial Proteins/genetics , Carbapenems , Cross Infection/epidemiology , Cross Infection/microbiology , Humans , Hydroxamic Acids/pharmacology , Klebsiella Infections/microbiology , Klebsiella pneumoniae/classification , Liver Abscess/epidemiology , Liver Abscess/microbiology , Molecular Epidemiology , Phylogeography , Serogroup , Urinary Tract Infections/epidemiology , Urinary Tract Infections/microbiology , Virulence
11.
Article in English | MEDLINE | ID: mdl-28348979

ABSTRACT

Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of ß-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized.


Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/pathogenicity , Drug Resistance, Multiple, Bacterial , Virulence Factors/metabolism , Animals , Biological Therapy/methods , Humans
12.
Appl Biochem Biotechnol ; 181(3): 961-971, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27743343

ABSTRACT

A novel ß-agarase AgaJ11 belonging to the glycoside hydrolase (GH) 16 family was identified from an agar-degrading bacterium Gayadomonas joobiniege G7. AgaJ11 was composed of 317 amino acids (35 kDa), including a 26-amino acid signal peptide, and had the highest similarity (44 % identity) to a putative ß-agarase from an agarolytic marine bacterium Agarivorans albus MKT 106. The agarase activity of purified AgaJ11 was confirmed by zymogram analysis. The optimum pH and temperature for AgaJ11 activity were determined to be 4.5 and 40 °C, respectively. Notably, AgaJ11 is an acidic ß-agarase that was active only at a narrow pH range from 4 to 5, and less than 30 % of its enzymatic activity was retained at other pH conditions. The K m and V max of AgaJ11 for agarose were 21.42 mg/ml and 25 U/mg, respectively. AgaJ11 did not require metal ions for its activity, but severe inhibition by several metal ions was observed. Thin layer chromatography and agarose-liquefying analyses revealed that AgaJ11 is an endo-type ß-agarase that hydrolyzes agarose into neoagarohexaose, neoagarotetraose, and neoagarobiose. Therefore, this study shows that AgaJ11 from G. joobiniege G7 is a novel GH16 ß-agarase with an acidic enzymatic feature that may be useful for industrial applications.


Subject(s)
Alteromonadaceae , Bacterial Proteins , Cloning, Molecular , Gene Expression , Glycoside Hydrolases , Alteromonadaceae/enzymology , Alteromonadaceae/genetics , Bacterial Proteins/biosynthesis , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Glycoside Hydrolases/biosynthesis , Glycoside Hydrolases/chemistry , Glycoside Hydrolases/genetics
13.
Biores Open Access ; 5(1): 192-200, 2016.
Article in English | MEDLINE | ID: mdl-27588219

ABSTRACT

This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs) and homogenized extracellular matrix (ECM) in the form of adipose stromal vascular fraction (SVF), along with hyaluronic acid (HA) and platelet-rich plasma (PRP) activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA) patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI) data, functional rating index, range of motion (ROM), and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees.

14.
Front Microbiol ; 7: 895, 2016.
Article in English | MEDLINE | ID: mdl-27379038

ABSTRACT

The emergence of carbapenem-resistant Gram-negative pathogens poses a serious threat to public health worldwide. In particular, the increasing prevalence of carbapenem-resistant Klebsiella pneumoniae is a major source of concern. K. pneumoniae carbapenemases (KPCs) and carbapenemases of the oxacillinase-48 (OXA-48) type have been reported worldwide. New Delhi metallo-ß-lactamase (NDM) carbapenemases were originally identified in Sweden in 2008 and have spread worldwide rapidly. In this review, we summarize the epidemiology of K. pneumoniae producing three carbapenemases (KPCs, NDMs, and OXA-48-like). Although the prevalence of each resistant strain varies geographically, K. pneumoniae producing KPCs, NDMs, and OXA-48-like carbapenemases have become rapidly disseminated. In addition, we used recently published molecular and genetic studies to analyze the mechanisms by which these three carbapenemases, and major K. pneumoniae clones, such as ST258 and ST11, have become globally prevalent. Because carbapenemase-producing K. pneumoniae are often resistant to most ß-lactam antibiotics and many other non-ß-lactam molecules, the therapeutic options available to treat infection with these strains are limited to colistin, polymyxin B, fosfomycin, tigecycline, and selected aminoglycosides. Although, combination therapy has been recommended for the treatment of severe carbapenemase-producing K. pneumoniae infections, the clinical evidence for this strategy is currently limited, and more accurate randomized controlled trials will be required to establish the most effective treatment regimen. Moreover, because rapid and accurate identification of the carbapenemase type found in K. pneumoniae may be difficult to achieve through phenotypic antibiotic susceptibility tests, novel molecular detection techniques are currently being developed.

15.
Sci Rep ; 6: 30642, 2016 07 29.
Article in English | MEDLINE | ID: mdl-27469068

ABSTRACT

Hemagglutinin (HA) from the influenza virus plays a pivotal role in the infection of host mammalian cells and is, therefore, a druggable target, similar to neuraminidase. However, research involving the influenza virus must be conducted in facilities certified at or above Biosafety Level 2 because of the potential threat of the contagiousness of this virus. To develop a new HA inhibitor screening system without intact influenza virus, we conceived a single-vesicle fusion assay using full-length recombinant HA. In this study, we first showed that full-length recombinant HA can mediate membrane fusion in ensemble and single-vesicle fusion assays. The fluorescence resonance energy transfer (FRET) frequency pattern of single-vesicle complexes completely differed when the inhibitors targeted the HA1 or HA2 domain of HA. This result indicates that analysing the FRET patterns in this assay can provide information regarding the domains of HA inhibited by compounds and compounds' inhibitory activities. Therefore, our results suggest that the assay developed here is a promising tool for the discovery of anti-influenza virus drug candidates as a new in vitro inhibitor screening system against HA from the influenza virus.


Subject(s)
Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Drug Evaluation, Preclinical/methods , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Orthomyxoviridae/drug effects , Fluorescence Resonance Energy Transfer , Membrane Fusion/drug effects
16.
Front Microbiol ; 6: 828, 2015.
Article in English | MEDLINE | ID: mdl-26322035

ABSTRACT

The increase of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) poses a worldwide and serious health threat. Although new antibiotics, such as daptomycin and linezolid, have been developed for the treatment of infections of Gram-positive pathogens, the emergence of daptomycin-resistant and linezolid-resistant strains during therapy has now increased clinical treatment failures. In the past few years, studies using quantitative proteomic methods have provided a considerable progress in understanding antibiotic resistance mechanisms. In this review, to understand the resistance mechanisms to four clinically important antibiotics (methicillin, vancomycin, linezolid, and daptomycin) used in the treatment of Gram-positive pathogens, we summarize recent advances in studies on resistance mechanisms using quantitative proteomic methods, and also examine proteins playing an important role in the bacterial mechanisms of resistance to the four antibiotics. Proteomic researches can identify proteins whose expression levels are changed in the resistance mechanism to only one antibiotic, such as LiaH in daptomycin resistance and PrsA in vancomycin resistance, and many proteins simultaneously involved in resistance mechanisms to various antibiotics. Most of resistance-related proteins, which are simultaneously associated with resistance mechanisms to several antibiotics, play important roles in regulating bacterial envelope biogenesis, or compensating for the fitness cost of antibiotic resistance. Therefore, proteomic data confirm that antibiotic resistance requires the fitness cost and the bacterial envelope is an important factor in antibiotic resistance.

17.
Int J Mol Sci ; 16(5): 9654-92, 2015 Apr 29.
Article in English | MEDLINE | ID: mdl-25938965

ABSTRACT

Carbapenems (imipenem, meropenem, biapenem, ertapenem, and doripenem) are ß-lactam antimicrobial agents. Because carbapenems have the broadest spectra among all ß-lactams and are primarily used to treat infections by multi-resistant Gram-negative bacteria, the emergence and spread of carbapenemases became a major public health concern. Carbapenemases are the most versatile family of ß-lactamases that are able to hydrolyze carbapenems and many other ß-lactams. According to the dependency of divalent cations for enzyme activation, carbapenemases can be divided into metallo-carbapenemases (zinc-dependent class B) and non-metallo-carbapenemases (zinc-independent classes A, C, and D). Many studies have provided various carbapenemase structures. Here we present a comprehensive and systematic review of three-dimensional structures of carbapenemase-carbapenem complexes as well as those of carbapenemases. We update recent studies in understanding the enzymatic mechanism of each class of carbapenemase, and summarize structural insights about regions and residues that are important in acquiring the carbapenemase activity.


Subject(s)
Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Drug Resistance, Microbial , beta-Lactamases/chemistry , beta-Lactamases/metabolism , Hydrolysis , Models, Molecular , Structure-Activity Relationship , Zinc/metabolism
18.
Biomed Res Int ; 2015: 214021, 2015.
Article in English | MEDLINE | ID: mdl-25945327

ABSTRACT

Widespread antimicrobial use and concomitant resistance have led to a significant threat to public health. Because inappropriate use and overuse of antibiotics based on insufficient knowledge are one of the major drivers of antibiotic resistance, education about prudent antibiotic use aimed at both the prescribers and the public is important. This review investigates recent studies on the effect of interventions for promoting prudent antibiotics prescribing. Up to now, most educational efforts have been targeted to medical professionals, and many studies showed that these educational efforts are significantly effective in reducing antibiotic prescribing. Recently, the development of educational programs to reduce antibiotic use is expanding into other groups, such as the adult public and children. The investigation of the contents of educational programs for prescribers and the public demonstrates that it is important to develop effective educational programs suitable for each group. In particular, it seems now to be crucial to develop appropriate curricula for teaching medical and nonmedical (pharmacy, dentistry, nursing, veterinary medicine, and midwifery) undergraduate students about general medicine, microbial virulence, mechanism of antibiotic resistance, and judicious antibiotic prescribing.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Patient Education as Topic , Practice Patterns, Physicians' , Humans
19.
Int J Environ Res Public Health ; 10(9): 4274-305, 2013 Sep 12.
Article in English | MEDLINE | ID: mdl-24036486

ABSTRACT

Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics.


Subject(s)
Drug Resistance, Microbial , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Bacterial Infections/drug therapy , Health Education , Health Personnel/education , Humans , Hygiene , Patient Education as Topic , Practice Patterns, Physicians' , Veterinary Medicine
20.
Curr Pharm Des ; 19(36): 6534-50, 2013.
Article in English | MEDLINE | ID: mdl-23829374

ABSTRACT

The rapid increase of human infections by multidrug-resistant (MDR) Gram-negative pathogens poses a serious health threat and demands the identification of new strategies, molecular targets, and agents for the treatment of Gram-negative bacterial infections. The biosynthesis of lipid A, the membrane-anchoring portion of lipopolysaccharide (LPS), is one promising target for novel antibiotic design because lipid A is essential for LPS assembly in most Gram-negative bacteria. The first three enzymes in the biosynthesis of lipid A, UDP-N-acetylglucosamine acyltransferase (LpxA), UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase (LpxC) and UDP- 3-O-(R-3-hydroxyacyl)glucosamine N-acyltransferase (LpxD), have emerged as an attractive Gram-negative antibacterial molecular target. In this article, we review recent advances in the studies on the structures and the structure-based drug designs of the three enzymes.


Subject(s)
Drug Design , Drug Resistance, Multiple/drug effects , Enzyme Inhibitors/pharmacology , Gram-Negative Bacteria/pathogenicity , Gram-Negative Bacterial Infections/drug therapy , Lipid A/biosynthesis , Acyltransferases/antagonists & inhibitors , Amidohydrolases/antagonists & inhibitors , Animals , Enzyme Inhibitors/chemistry , Gram-Negative Bacteria/drug effects , Gram-Negative Bacterial Infections/microbiology , Humans
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