The Activity of Glycopeptide Antibiotics against Resistant Bacteria Correlates with Their Ability To Induce the Resistance System

ABSTRACTGlycopeptide antibiotics containing a hydrophobic substituent display the best activity against vancomycin-resistant enterococci, and they have been assumed to be poor inducers of the resistance system. Using a panel of 26 glycopeptide derivatives and the model resistance system inStreptomyces coelicolor, we confirmed this hypothesis at the level of transcription. Identification of the structural glycopeptide features associated with inducing the expression of resistance genes has important implications in the search for more effective antibiotic structures.

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Oritavancin Activity against Vancomycin-Susceptible and Vancomycin-Resistant Enterococci with Molecularly Characterized Glycopeptide Resistance Genes Recovered from Bacteremic Patients, 2009-2010

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.06067-11 ◽

2011 ◽

Vol 56 (3) ◽

pp. 1639-1642 ◽

Cited By ~ 23

Author(s):

Rodrigo E. Mendes ◽

Leah N. Woosley ◽

David J. Farrell ◽

Helio S. Sader ◽

Ronald N. Jones

Keyword(s):

Resistance Genes ◽

Glycopeptide Resistance ◽

Content Type ◽

Vancomycin Resistant Enterococci ◽

Vancomycin Resistant

ABSTRACTOritavancin exhibited potent activity against vancomycin-susceptible (MIC50and MIC90, 0.015/0.03 μg/ml) andvanB-carryingE. faecalisisolates (MIC50and MIC90, 0.015 and 0.015 μg/ml). Higher (16- to 32-fold) MIC50s and MIC90s forvanA-harboringE. faecaliswere noted (MIC50and MIC90, 0.25 and 0.5 μg/ml), although oritavancin inhibited all strains at ≤0.5 μg/ml. Vancomycin-susceptible andvanB-carryingE. faeciumstrains (MIC50and MIC90, ≤0.008 and ≤0.008 μg/ml for both) were very susceptible to oritavancin, as were VanA-producing isolates (MIC50and MIC90, 0.03 and 0.06 μg/ml). Oritavancin exhibited goodin vitropotency against this collection of organisms, including vancomycin-resistant enterococci.

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A Phenotypically Silent vanB2 Operon Carried on a Tn1549-Like Element in Clostridium difficile

mSphere ◽

10.1128/msphere.00177-16 ◽

2016 ◽

Vol 1 (4) ◽

Cited By ~ 13

Author(s):

Daniel R. Knight ◽

Grace O. Androga ◽

Susan A. Ballard ◽

Benjamin P. Howden ◽

Thomas V. Riley

Keyword(s):

Health Care ◽

Clostridium Difficile ◽

Resistance Genes ◽

Vancomycin Resistance ◽

Content Type ◽

Vancomycin Resistant Enterococci ◽

Vancomycin Resistant ◽

Emergence Of Resistance ◽

First Time

ABSTRACT In an era when the development of new antimicrobial drugs is slow, vancomycin remains the preferred antimicrobial therapy for Clostridium difficile infection (CDI), the most important health care-related infection in the world today. The emergence of resistance to vancomycin would have significant consequences in relation to treating patients with CDI. In this paper, we describe for the first time a complete set of vancomycin resistance genes in C. difficile. The genes were very similar to genes found in vancomycin-resistant enterococci (VRE) that were associated with the emergence and global dissemination of this organism. Fortunately, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly because of a small difference in one gene. However, this observation signals that we may be very close to seeing a fully vancomycin-resistant strain of C. difficile. In the last decade, Clostridium difficile infection (CDI) has reached an epidemic state with increasing incidence and severity in both health care and community settings. Vancomycin is an important first-line therapy for CDI, and the emergence of resistance would have significant clinical consequences. In this study, we describe for the first time a vanB2 vancomycin resistance operon in C. difficile, isolated from an Australian veal calf at slaughter. The operon was carried on an ~42-kb element showing significant homology and synteny to Tn1549, a conjugative transposon linked with the emergence and global dissemination of vancomycin-resistant enterococci (VRE). Notably, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly as a result of an aberrant vanRB gene. As observed for other anaerobic species of the animal gut microbiota, C. difficile may be a reservoir of clinically important vancomycin resistance genes. IMPORTANCE In an era when the development of new antimicrobial drugs is slow, vancomycin remains the preferred antimicrobial therapy for Clostridium difficile infection (CDI), the most important health care-related infection in the world today. The emergence of resistance to vancomycin would have significant consequences in relation to treating patients with CDI. In this paper, we describe for the first time a complete set of vancomycin resistance genes in C. difficile. The genes were very similar to genes found in vancomycin-resistant enterococci (VRE) that were associated with the emergence and global dissemination of this organism. Fortunately, the C. difficile strain did not show any reduced susceptibility to vancomycin in vitro (MIC, 1 mg/liter), possibly because of a small difference in one gene. However, this observation signals that we may be very close to seeing a fully vancomycin-resistant strain of C. difficile.

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Glycopeptide Antibiotic Resistance Genes in Glycopeptide-Producing Organisms

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.9.2215 ◽

1998 ◽

Vol 42 (9) ◽

pp. 2215-2220 ◽

Cited By ~ 157

Author(s):

C. G. Marshall ◽

I. A. D. Lessard ◽

I.-S. Park ◽

G. D. Wright

Keyword(s):

Resistance Genes ◽

Resistance Mechanism ◽

Antibiotic Resistance Genes ◽

Amino Acid Sequences ◽

Glycopeptide Antibiotics ◽

Degenerate Primers ◽

Vancomycin Resistant Enterococci ◽

Genes Encoding ◽

Vancomycin Resistant ◽

High Level

ABSTRACT The mechanism of high-level resistance to vancomycin in enterococci consists of the synthesis of peptidoglycan terminating ind-alanyl-d-lactate instead of the usuald-alanyl-d-alanine. This alternate cell wall biosynthesis pathway is ensured by the collective actions of three enzymes: VanH, VanA, and VanX. The origin of this resistance mechanism is unknown. We have cloned three genes encoding homologs of VanH, VanA, and VanX from two organisms which produce glycopeptide antibiotics: the A47934 producer Streptomyces toyocaensis NRRL 15009 and the vancomycin producer Amycolatopsis orientalis C329.2. The predicted amino acid sequences are highly similar to those found in VRE: 54 to 61% identity for VanH, 59 to 63% identity for VanA, and 61 to 64% identity for VanX. Furthermore, the orientations of the genes,vanH, vanA, and vanX, are identical to the orientations found in vancomycin-resistant enterococci. Southern analysis of total DNA from other glycopeptide-producing organisms,A. orientalis 18098 (chloro-eremomycin producer), A. orientalis subsp. lurida (ristocetin producer), andAmycolatopsis coloradensis subsp. labeda(teicoplanin and avoparcin producer), with a probe derived from thevanH, vanA, and vanX cluster fromA. orientalis C329.2 revealed cross-hybridizing DNA in all strains. In addition, the vanH, vanA,vanX cluster was amplified from all glycopeptide-producing organisms by PCR with degenerate primers complementary to conserved regions in VanH and VanX. Thus, this gene sequence is common to all glycopeptide producers tested. These results suggest that glycopeptide-producing organisms may have been the source of resistance genes in vancomycin-resistant enterococci.

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Prevalence of Vancomycin-Resistant Enterococci and Antimicrobial Residues in Wastewater and Surface Water

Life ◽

10.3390/life11121403 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1403

Author(s):

Kristýna Hricová ◽

Magdaléna Röderová ◽

Petr Fryčák ◽

Volodymyr Pauk ◽

Ondřej Kurka ◽

...

Keyword(s):

Surface Water ◽

Resistance Genes ◽

Water Samples ◽

Antimicrobial Agents ◽

Wastewater Treatment Plants ◽

Resistant Bacteria ◽

Vancomycin Resistant Enterococci ◽

Vancomycin Resistant ◽

Wastewater Samples ◽

Surface Water Samples

Due to the extensive use of antimicrobial agents in human and veterinary medicine, residues of various antimicrobials get into wastewater and, subsequently, surface water. On the one hand, a combination of processes in wastewater treatment plants aims to eliminate chemical and biological pollutants; on the other hand, this environment may create conditions suitable for the horizontal transfer of resistance genes and potential selection of antibiotic-resistant bacteria. Wastewater and surface water samples (Morava River) were analyzed to determine the concentrations of 10 antibiotics and identify those exceeding so-called predicted no-effect environmental concentrations (PNECs). This study revealed that residues of five of the tested antimicrobials, namely ampicillin, clindamycin, tetracycline, tigecycline and vancomycin, in wastewater samples exceeded the PNEC. Vancomycin concentrations were analyzed with respect to the detected strains of vancomycin-resistant enterococci (VRE), in which the presence of resistance genes, virulence factors and potential relationship were analyzed. VRE were detected in 16 wastewater samples (11%) and two surface water samples (6%). The PNEC of vancomycin was exceed in 16% of the samples. Since the detected VRE did not correlate with the vancomycin concentrations, no direct relationship was confirmed between the residues of this antimicrobials and the presence of the resistant strains.

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Environmental Spread of New Delhi Metallo-β-Lactamase-1-Producing Multidrug-Resistant Bacteria in Dhaka, Bangladesh

Applied and Environmental Microbiology ◽

10.1128/aem.00793-17 ◽

2017 ◽

Vol 83 (15) ◽

Cited By ~ 32

Author(s):

Mohammad Aminul Islam ◽

Moydul Islam ◽

Rashedul Hasan ◽

M. Iqbal Hossain ◽

Ashikun Nabi ◽

...

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Tap Water ◽

Antibiotic Resistance Genes ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

New Delhi ◽

Multidrug Resistant Bacteria ◽

Content Type ◽

Wastewater Samples

ABSTRACT Resistance to carbapenem antibiotics through the production of New Delhi metallo-β-lactamase-1 (NDM-1) constitutes an emerging challenge in the treatment of bacterial infections. To monitor the possible source of the spread of these organisms in Dhaka, Bangladesh, we conducted a comparative analysis of wastewater samples from hospital-adjacent areas (HAR) and from community areas (COM), as well as public tap water samples, for the occurrence and characteristics of NDM-1-producing bacteria. Of 72 HAR samples tested, 51 (71%) samples were positive for NDM-1-producing bacteria, as evidenced by phenotypic tests and the presence of the bla NDM-1 gene, compared to 5 of 41 (12.1%) samples from COM samples (P < 0.001). All tap water samples were negative for NDM-1-producing bacteria. Klebsiella pneumoniae (44%) was the predominant bacterial species among bla NDM-1-positive isolates, followed by Escherichia coli (29%), Acinetobacter spp. (15%), and Enterobacter spp. (9%). These bacteria were also positive for one or more other antibiotic resistance genes, including bla CTX-M-1 (80%), bla CTX-M-15 (63%), bla TEM (76%), bla SHV (33%), bla CMY-2 (16%), bla OXA-48-like (2%), bla OXA-1 (53%), and bla OXA-47-like (60%) genes. Around 40% of the isolates contained a qnr gene, while 50% had 16S rRNA methylase genes. The majority of isolates hosted multiple plasmids, and plasmids of 30 to 50 MDa carrying bla NDM-1 were self-transmissible. Our results highlight a number of issues related to the characteristics and source of spread of multidrug-resistant bacteria as a potential public health threat. In view of the existing practice of discharging untreated liquid waste into the environment, hospitals in Dhaka city contribute to the potential dissemination of NDM-1-producing bacteria into the community. IMPORTANCE Infections caused by carbapenemase-producing Enterobacteriaceae are extremely difficult to manage due to their marked resistance to a wide range of antibiotics. NDM-1 is the most recently described carbapenemase, and the bla NDM-1 gene, which encodes NDM-1, is located on self-transmissible plasmids that also carry a considerable number of other antibiotic resistance genes. The present study shows a high prevalence of NDM-1-producing organisms in the wastewater samples from hospital-adjacent areas as a potential source for the spread of these organisms to community areas in Dhaka, Bangladesh. The study also examines the characteristics of the isolates and their potential to horizontally transmit the resistance determinants. The significance of our research is in identifying the mode of spread of multiple-antibiotic-resistant organisms, which will allow the development of containment measures, leading to broader impacts in reducing their spread to the community.

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Activities of Oxadiazole Antibacterials against Staphylococcus aureus and Other Gram-Positive Bacteria

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00453-18 ◽

2018 ◽

Vol 62 (8) ◽

Cited By ~ 2

Author(s):

Sara Ceballos ◽

Choon Kim ◽

Derong Ding ◽

Shahriar Mobashery ◽

Mayland Chang ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Gram Positive ◽

Methicillin Resistant ◽

Content Type ◽

Gram Positive Bacteria ◽

Vancomycin Resistant Enterococci ◽

Vancomycin Resistant ◽

Mrsa Strains

ABSTRACT The activities of four oxadiazoles were investigated with 210 methicillin-resistant Staphylococcus aureus (MRSA) strains. MIC50 and MIC90 values of 1 to 2 and 4 μg/ml, respectively, were observed. We also evaluated the activity of oxadiazole ND-421 against other staphylococci and enterococci and in the presence of oxacillin for selected MRSA strains. The MIC for ND-421 is lowered severalfold in combination with oxacillin, as they synergize. The MIC90 of ND-421 against vancomycin-resistant enterococci is ≤1 μg/ml.

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Merging Metagenomics and Spatial Epidemiology To Understand the Distribution of Antimicrobial Resistance Genes from Enterobacteriaceae in Wild Owls

Applied and Environmental Microbiology ◽

10.1128/aem.00571-20 ◽

2020 ◽

Vol 86 (20) ◽

Author(s):

Elizabeth A. Miller ◽

Julia B. Ponder ◽

Michelle Willette ◽

Timothy J. Johnson ◽

Kimberly L. VanderWaal

Keyword(s):

Antimicrobial Resistance ◽

Resistance Genes ◽

Spatial Epidemiology ◽

Anthropogenic Sources ◽

Resistant Bacteria ◽

Metagenomic Sequencing ◽

Wild Animals ◽

Natural Ecosystems ◽

Content Type ◽

Antimicrobial Resistance Genes

ABSTRACT Antimicrobial resistance (AMR) is a well-documented phenomenon in bacteria from many natural ecosystems, including wild animals. However, the specific determinants and spatial distribution of resistant bacteria and antimicrobial resistance genes (ARGs) in the environment remain incompletely understood. In particular, information regarding the importance of anthropogenic sources of AMR relative to that of other biological and ecological influences is lacking. We conducted a cross-sectional study of AMR in great horned owls (Bubo virginianus) and barred owls (Strix varia) admitted to a rehabilitation center in the midwestern United States. A combination of selective culture enrichment and shotgun metagenomic sequencing was used to identify ARGs from Enterobacteriaceae. Overall, the prevalence of AMR was comparable to that in past studies of resistant Enterobacteriaceae in raptors, with acquired ARGs being identified in 23% of samples. Multimodel regression analyses identified seasonality and owl age to be important predictors of the likelihood of the presence of ARGs, with birds sampled during warmer months being more likely to harbor ARGs than those sampled during cooler months and with birds in their hatch year being more likely to harbor β-lactam ARGs than adults. Beyond host-specific determinants, ARG-positive owls were also more likely to be recovered from areas of high agricultural land cover. Spatial clustering analyses identified a significant high-risk cluster of tetracycline resistance gene-positive owls in the southern sampling range, but this could not be explained by any predictor variables. Taken together, these results highlight the complex distribution of AMR in natural environments and suggest that both biological and anthropogenic factors play important roles in determining the emergence and persistence of AMR in wildlife. IMPORTANCE Antimicrobial resistance (AMR) is a multifaceted problem that poses a worldwide threat to human and animal health. Recent reports suggest that wildlife may play an important role in the emergence, dissemination, and persistence of AMR. As such, there have been calls for better integration of wildlife into current research on AMR, including the use of wild animals as biosentinels of AMR contamination in the environment. A One Health approach can be used to gain a better understanding of all AMR sources and pathways, particularly those at the human-animal-environment interface. Our study focuses on this interface in order to assess the effect of human-impacted landscapes on AMR in a wild animal. This work highlights the value of wildlife rehabilitation centers for environmental AMR surveillance and demonstrates how metagenomic sequencing within a spatial epidemiology framework can be used to address questions surrounding AMR complexity in natural ecosystems.

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High Colonization Rate and Heterogeneity of ESBL- and Carbapenemase-Producing Enterobacteriaceae Isolated from Gull Feces in Lisbon, Portugal

Microorganisms ◽

10.3390/microorganisms8101487 ◽

2020 ◽

Vol 8 (10) ◽

pp. 1487

Author(s):

Marta Aires-de-Sousa ◽

Claudine Fournier ◽

Elizeth Lopes ◽

Hermínia de Lencastre ◽

Patrice Nordmann ◽

...

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Bacterial Species ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Multidrug Resistant Bacteria ◽

Vancomycin Resistant Enterococci ◽

Vancomycin Resistant ◽

Encoding Genes

In order to evaluate whether seagulls living on the Lisbon coastline, Portugal, might be colonized and consequently represent potential spreaders of multidrug-resistant bacteria, a total of 88 gull fecal samples were screened for detection of extended-spectrum β-lactamase (ESBL)- or carbapenemase-producing Enterobacteriaceae for methicillin-resistant Staphylococcus aureus (MRSA) and for vancomycin-resistant Enterococci (VRE). A large proportion of samples yielded carbapenemase- or ESBL-producing Enterobacteriaceae (16% and 55%, respectively), while only two MRSA and two VRE were detected. Mating-out assays followed by PCR and whole-plasmid sequencing allowed to identify carbapenemase and ESBL encoding genes. Among 24 carbapenemase-producing isolates, there were mainly Klebsiella pneumoniae (50%) and Escherichia coli (33%). OXA-181 was the most common carbapenemase identified (54%), followed by OXA-48 (25%) and KPC-2 (17%). Ten different ESBLs were found among 62 ESBL-producing isolates, mainly being CTX-M-type enzymes (87%). Co-occurrence in single samples of multiple ESBL- and carbapenemase producers belonging to different bacterial species was observed in some cases. Seagulls constitute an important source for spreading multidrug-resistant bacteria in the environment and their gut microbiota a formidable microenvironment for transfer of resistance genes within bacterial species.

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ESKAPE Bacteria and Extended-Spectrum-β-Lactamase-Producing Escherichia coli Isolated from Wastewater and Process Water from German Poultry Slaughterhouses

Applied and Environmental Microbiology ◽

10.1128/aem.02748-19 ◽

2020 ◽

Vol 86 (8) ◽

Cited By ~ 7

Author(s):

Mykhailo Savin ◽

Gabriele Bierbaum ◽

Jens Andre Hammerl ◽

Céline Heinemann ◽

Marijo Parcina ◽

...

Keyword(s):

Escherichia Coli ◽

Wastewater Treatment ◽

Resistance Genes ◽

Wastewater Treatment Plants ◽

Process Water ◽

Resistant Bacteria ◽

Content Type ◽

E Coli ◽

Extended Spectrum ◽

Clinically Relevant Bacteria

ABSTRACT The wastewater of livestock slaughterhouses is considered a source of antimicrobial-resistant bacteria with clinical relevance and may thus be important for their dissemination into the environment. To get an overview of their occurrence and characteristics, we investigated process water (n = 50) from delivery and unclean areas as well as wastewater (n = 32) from the in-house wastewater treatment plants (WWTPs) of two German poultry slaughterhouses (slaughterhouses S1 and S2). The samples were screened for ESKAPE bacteria (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) and Escherichia coli. Their antimicrobial resistance phenotypes and the presence of extended-spectrum-β-lactamase (ESBL), carbapenemase, and mobilizable colistin resistance genes were determined. Selected ESKAPE bacteria were epidemiologically classified using different molecular typing techniques. At least one of the target species was detected in 87.5% (n = 28/32) of the wastewater samples and 86.0% (n = 43/50) of the process water samples. The vast majority of the recovered isolates (94.9%, n = 448/472) was represented by E. coli (39.4%), the A. calcoaceticus-A. baumannii (ACB) complex (32.4%), S. aureus (12.3%), and K. pneumoniae (10.8%), which were widely distributed in the delivery and unclean areas of the individual slaughterhouses, including their wastewater effluents. Enterobacter spp., Enterococcus spp., and P. aeruginosa were less abundant and made up 5.1% of the isolates. Phenotypic and genotypic analyses revealed that the recovered isolates exhibited diverse resistance phenotypes and β-lactamase genes. In conclusion, wastewater effluents from the investigated poultry slaughterhouses exhibited clinically relevant bacteria (E. coli, methicillin-resistant S. aureus, K. pneumoniae, and species of the ACB and Enterobacter cloacae complexes) that contribute to the dissemination of clinically relevant resistances (i.e., blaCTX-M or blaSHV and mcr-1) in the environment. IMPORTANCE Bacteria from livestock may be opportunistic pathogens and carriers of clinically relevant resistance genes, as many antimicrobials are used in both veterinary and human medicine. They may be released into the environment from wastewater treatment plants (WWTPs), which are influenced by wastewater from slaughterhouses, thereby endangering public health. Moreover, process water that accumulates during the slaughtering of poultry is an important reservoir for livestock-associated multidrug-resistant bacteria and may serve as a vector of transmission to occupationally exposed slaughterhouse employees. Mitigation solutions aimed at the reduction of the bacterial discharge into the production water circuit as well as interventions against their further transmission and dissemination need to be elaborated. Furthermore, the efficacy of in-house WWTPs needs to be questioned. Reliable data on the occurrence and diversity of clinically relevant bacteria within the slaughtering production chain and in the WWTP effluents in Germany will help to assess their impact on public and environmental health.

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New Gram-Positive Agents: the Next Generation of Oxazolidinones and Lipoglycopeptides

Journal of Clinical Microbiology ◽

10.1128/jcm.03395-15 ◽

2016 ◽

Vol 54 (9) ◽

pp. 2225-2232 ◽

Cited By ~ 23

Author(s):

Matthew P. Crotty ◽

Tamara Krekel ◽

Carey-Ann D. Burnham ◽

David J. Ritchie

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Resistance ◽

Next Generation ◽

Gram Positive ◽

Content Type ◽

Skin Structure ◽

Vancomycin Resistant Enterococci ◽

Vancomycin Resistant ◽

The U.S

The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistantStaphylococcus aureus(MRSA) and vancomycin-resistant enterococci (VRE), has reached a critical state. Tedizolid phosphate, dalbavancin, and oritavancin have recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and represent the next generation of oxazolidinones and lipoglycopeptides. All three agents exhibitin vitroactivity and clinical efficacy against MRSA. Tedizolid phosphate and oritavancin demonstratein vitroactivity against VRE. These new Gram-positive agents are reviewed here.

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