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12 pages, 2816 KiB

Open AccessArticle

Evaluation of Chemical Changes in Laboratory-Induced Colistin-Resistant Klebsiella pneumoniae

by Agata Pruss, Paweł Kwiatkowski, Łukasz Łopusiewicz, Helena Masiuk, Peter Sobolewski, Karol Fijałkowski, Monika Sienkiewicz, Adam Smolak, Stefania Giedrys-Kalemba and Barbara Dołęgowska

Int. J. Mol. Sci. 2021, 22(13), 7104; https://doi.org/10.3390/ijms22137104 - 1 Jul 2021

Cited by 5 | Viewed by 3184

Abstract

This study evaluates the electrical potential and chemical alterations in laboratory-induced colistin-resistant Klebsiella pneumoniae, as compared to the susceptible strain using spectroscopic analyses. The minimal inhibitory concentration (MIC) of colistin, ζ-potential and chemical composition analysis of K. pneumoniae strains are determined. The [...] Read more.

This study evaluates the electrical potential and chemical alterations in laboratory-induced colistin-resistant Klebsiella pneumoniae, as compared to the susceptible strain using spectroscopic analyses. The minimal inhibitory concentration (MIC) of colistin, ζ-potential and chemical composition analysis of K. pneumoniae strains are determined. The results obtained for the K. pneumoniae^Col-R with induced high-level colistin resistance (MIC = 16.0 ± 0.0 mg/L) are compared with the K. pneumoniae^Col-S strain susceptible to colistin (MIC = 0.25 ± 0.0 mg/L). Fourier transform infrared (FTIR) and Raman spectroscopic studies revealed differences in bacterial cell wall structures and lipopolysaccharide (LPS) of K. pneumoniae^Col-R and K. pneumoniae^Col-S strains. In the beginning, we assumed that the obtained results could relate to a negative charge of the bacterial surface and different electrostatic interactions with cationic antibiotic molecules, reducing the affinity of colistin and leading to its lower penetration into K. pneumoniae^Col-R cell. However, no significant differences in the ζ-potential between the K. pneumoniae^Col-R and K. pneumoniae^Col-S strains are noticed. In conclusion, this mechanism is most probably associated with recognisable changes in the chemical composition of the K. pneumoniae^Col-R cell wall (especially in LPS) when compared to the susceptible strain. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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18 pages, 2450 KiB

Open AccessArticle

Structural Modifications of the Quinolin-4-yloxy Core to Obtain New Staphylococcus aureus NorA Inhibitors

by Rolando Cannalire, Gianmarco Mangiaterra, Tommaso Felicetti, Andrea Astolfi, Nicholas Cedraro, Serena Massari, Giuseppe Manfroni, Oriana Tabarrini, Salvatore Vaiasicca, Maria Letizia Barreca, Violetta Cecchetti, Francesca Biavasco and Stefano Sabatini

Int. J. Mol. Sci. 2020, 21(19), 7037; https://doi.org/10.3390/ijms21197037 - 24 Sep 2020

Cited by 9 | Viewed by 3245

Abstract

Tackling antimicrobial resistance (AMR) represents a social responsibility aimed at renewing the antimicrobial armamentarium and identifying novel therapeutical approaches. Among the possible strategies, efflux pumps inhibition offers the advantage to contrast the resistance against all drugs which can be extruded. Efflux pump inhibitors [...] Read more.

Tackling antimicrobial resistance (AMR) represents a social responsibility aimed at renewing the antimicrobial armamentarium and identifying novel therapeutical approaches. Among the possible strategies, efflux pumps inhibition offers the advantage to contrast the resistance against all drugs which can be extruded. Efflux pump inhibitors (EPIs) are molecules devoid of any antimicrobial activity, but synergizing with pumps-substrate antibiotics. Herein, we performed an in silico scaffold hopping approach starting from quinolin-4-yloxy-based Staphylococcus aureus NorA EPIs by using previously built pharmacophore models for NorA inhibition activity. Four scaffolds were identified, synthesized, and modified with appropriate substituents to obtain new compounds, that were evaluated for their ability to inhibit NorA and synergize with the fluoroquinolone ciprofloxacin against resistant S. aureus strains. The two quinoline-4-carboxamide derivatives 3a and 3b showed the best results being synergic (4-fold MIC reduction) with ciprofloxacin at concentrations as low as 3.13 and 1.56 µg/mL, respectively, which were nontoxic for human THP-1 and A549 cells. The NorA inhibition was confirmed by SA-1199B ethidium bromide efflux and checkerboard assays against the isogenic pair SA-K2378 (norA++)/SA-K1902 (norA-). These in vitro results indicate the two compounds as valuable structures for designing novel S. aureus NorA inhibitors to be used in association with fluoroquinolones. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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11 pages, 2253 KiB

Open AccessArticle

Epidemiologic, Phenotypic, and Structural Characterization of Aminoglycoside-Resistance Gene aac(3)-IV

by Michel Plattner, Marina Gysin, Klara Haldimann, Katja Becker and Sven N. Hobbie

Int. J. Mol. Sci. 2020, 21(17), 6133; https://doi.org/10.3390/ijms21176133 - 25 Aug 2020

Cited by 21 | Viewed by 4217

Abstract

Aminoglycoside antibiotics are powerful bactericidal therapeutics that are often used in the treatment of critical Gram-negative systemic infections. The emergence and global spread of antibiotic resistance, however, has compromised the clinical utility of aminoglycosides to an extent similar to that found for all [...] Read more.

Aminoglycoside antibiotics are powerful bactericidal therapeutics that are often used in the treatment of critical Gram-negative systemic infections. The emergence and global spread of antibiotic resistance, however, has compromised the clinical utility of aminoglycosides to an extent similar to that found for all other antibiotic-drug classes. Apramycin, a drug candidate currently in clinical development, was suggested as a next-generation aminoglycoside antibiotic with minimal cross-resistance to all other standard-of-care aminoglycosides. Here, we analyzed 591,140 pathogen genomes deposited in the NCBI National Database of Antibiotic Resistant Organisms (NDARO) for annotations of apramycin-resistance genes, and compared them to the genotypic prevalence of carbapenem resistance and 16S-rRNA methyltransferase (RMTase) genes. The 3-N-acetyltransferase gene aac(3)-IV was found to be the only apramycin-resistance gene of clinical relevance, at an average prevalence of 0.7%, which was four-fold lower than that of RMTase genes. In the important subpopulation of carbapenemase-positive isolates, aac(3)-IV was nine-fold less prevalent than RMTase genes. The phenotypic profiling of selected clinical isolates and recombinant strains expressing the aac(3)-IV gene confirmed resistance to not only apramycin, but also gentamicin, tobramycin, and paromomycin. Probing the structure–activity relationship of such substrate promiscuity by site-directed mutagenesis of the aminoglycoside-binding pocket in the acetyltransferase AAC(3)-IV revealed the molecular contacts to His124, Glu185, and Asp187 to be equally critical in binding to apramycin and gentamicin, whereas Asp67 was found to be a discriminating contact. Our findings suggest that aminoglycoside cross-resistance to apramycin in clinical isolates is limited to the substrate promiscuity of a single gene, rendering apramycin best-in-class for the coverage of carbapenem- and aminoglycoside-resistant bacterial infections. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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23 pages, 1561 KiB

Open AccessArticle

Tracking Antimicrobial Resistance Determinants in Diarrheal Pathogens: A Cross-Institutional Pilot Study

by Chris R. Taitt, Tomasz A. Leski, Michael G. Prouty, Gavin W. Ford, Vireak Heang, Brent L. House, Samuel Y. Levin, Jennifer A. Curry, Adel Mansour, Hanan El Mohammady, Momtaz Wasfy, Drake Hamilton Tilley, Michael J. Gregory, Matthew R. Kasper, James Regeimbal, Paul Rios, Guillermo Pimentel, Brook A. Danboise, Christine E. Hulseberg, Elizabeth A. Odundo, Abigael N. Ombogo, Erick K. Cheruiyot, Cliff O. Philip and Gary J. Vora Show full author list Hide full author list

Int. J. Mol. Sci. 2020, 21(16), 5928; https://doi.org/10.3390/ijms21165928 - 18 Aug 2020

Cited by 7 | Viewed by 4186

Abstract

Infectious diarrhea affects over four billion individuals annually and causes over a million deaths each year. Though not typically prescribed for treatment of uncomplicated diarrheal disease, antimicrobials serve as a critical part of the armamentarium used to treat severe or persistent cases. Due [...] Read more.

Infectious diarrhea affects over four billion individuals annually and causes over a million deaths each year. Though not typically prescribed for treatment of uncomplicated diarrheal disease, antimicrobials serve as a critical part of the armamentarium used to treat severe or persistent cases. Due to widespread over- and misuse of antimicrobials, there has been an alarming increase in global resistance, for which a standardized methodology for geographic surveillance would be highly beneficial. To demonstrate that a standardized methodology could be used to provide molecular surveillance of antimicrobial resistance (AMR) genes, we initiated a pilot study to test 130 diarrheal pathogens (Campylobacter spp., Escherichia coli, Salmonella, and Shigella spp.) from the USA, Peru, Egypt, Cambodia, and Kenya for the presence/absence of over 200 AMR determinants. We detected a total of 55 different determinants conferring resistance to ten different categories of antimicrobials: genes detected in ≥ 25 samples included bla_TEM, tet(A), tet(B), mac(A), mac(B), aadA1/A2, strA, strB, sul1, sul2, qacEΔ1, cmr, and dfrA1. The number of determinants per strain ranged from none (several Campylobacter spp. strains) to sixteen, with isolates from Egypt harboring a wider variety and greater number of genes per isolate than other sites. Two samples harbored carbapenemase genes, bla_OXA-48 or bla_NDM. Genes conferring resistance to azithromycin (ere(A), mph(A)/mph(K), erm(B)), a first-line therapeutic for severe diarrhea, were detected in over 10% of all Enterobacteriaceae tested: these included >25% of the Enterobacteriaceae from Egypt and Kenya. Forty-six percent of the Egyptian Enterobacteriaceae harbored genes encoding CTX-M-1 or CTX-M-9 families of extended-spectrum β-lactamases. Overall, the data provide cross-comparable resistome information to establish regional trends in support of international surveillance activities and potentially guide geospatially informed medical care. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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14 pages, 852 KiB

Open AccessArticle

New Determinants of Aminoglycoside Resistance and Their Association with the Class 1 Integron Gene Cassettes in Trueperella pyogenes

by Ewelina Kwiecień, Ilona Stefańska, Dorota Chrobak-Chmiel, Agnieszka Sałamaszyńska-Guz and Magdalena Rzewuska

Int. J. Mol. Sci. 2020, 21(12), 4230; https://doi.org/10.3390/ijms21124230 - 13 Jun 2020

Cited by 13 | Viewed by 4378

Abstract

Trueperella pyogenes is an important opportunistic animal pathogen. Different antimicrobials, including aminoglycosides, are used to treat T. pyogenes infections. The aim of the present study was to evaluate aminoglycoside susceptibility and to detect aminoglycoside resistance determinants in 86 T. pyogenes isolates of different [...] Read more.

Trueperella pyogenes is an important opportunistic animal pathogen. Different antimicrobials, including aminoglycosides, are used to treat T. pyogenes infections. The aim of the present study was to evaluate aminoglycoside susceptibility and to detect aminoglycoside resistance determinants in 86 T. pyogenes isolates of different origin. Minimum inhibitory concentration of gentamicin, streptomycin, and kanamycin was determined using a standard broth microdilution method. Genetic elements associated with aminoglycoside resistance were investigated by PCR and DNA sequencing. All studied isolates were susceptible to gentamicin, but 32.6% and 11.6% of them were classified as resistant to streptomycin and kanamycin, respectively. A total of 30 (34.9%) isolates contained class 1 integrons. Class 1 integron gene cassettes carrying aminoglycoside resistance genes, aadA11 and aadA9, were found in seven and two isolates, respectively. Additionally, the aadA9 gene found in six isolates was not associated with mobile genetic elements. Moreover, other, not carried by gene cassettes, aminoglycoside resistance genes, strA-strB and aph(3’)-IIIa, were also detected. Most importantly, this is the first description of all reported genes in T. pyogenes. Nevertheless, the relevance of the resistance phenotype to genotype was not perfectly matched in 14 isolates. Therefore, further investigations are needed to fully explain aminoglycoside resistance mechanisms in T. pyogenes. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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14 pages, 1937 KiB

Open AccessArticle

Antibiotic Susceptibility Profiles of Lactic Acid Bacteria from the Human Vagina and Genetic Basis of Acquired Resistances

by Auttawit Sirichoat, Ana Belén Flórez, Lucía Vázquez, Pranom Buppasiri, Marutpong Panya, Viraphong Lulitanond and Baltasar Mayo

Int. J. Mol. Sci. 2020, 21(7), 2594; https://doi.org/10.3390/ijms21072594 - 8 Apr 2020

Cited by 34 | Viewed by 6393

Abstract

Lactic acid bacteria can act as reservoirs of antibiotic resistance genes that can be ultimately transferred to pathogens. The present work reports on the minimum inhibitory concentration (MIC) of 16 antibiotics to 25 LAB isolates of five Lactobacillus and one Bifidobacterium species from [...] Read more.

Lactic acid bacteria can act as reservoirs of antibiotic resistance genes that can be ultimately transferred to pathogens. The present work reports on the minimum inhibitory concentration (MIC) of 16 antibiotics to 25 LAB isolates of five Lactobacillus and one Bifidobacterium species from the human vagina. Acquired resistances were detected to kanamycin, streptomycin, chloramphenicol, gentamicin, and ampicillin. A PCR analysis of lactobacilli failed to identify genetic determinants involved in any of these resistances. Surprisingly, a tet(W) gene was detected by PCR in two Bifidobacterium bifidum strains, although they proved to be tetracycline-susceptible. In agreement with the PCR results, no acquired genes were identified in the genome of any of the Lactobacillus spp. strains sequenced. A genome analysis of B. bifidum VA07-1AN showed an insertion of two guanines in the middle of tet(W) interrupting the open reading frame. By growing the strain in the presence of tetracycline, stable tetracycline-resistant variants were obtained. An amino acid substitution in the ribosomal protein S12 (K43R) was further identified as the most likely cause of VA07-1AN being streptomycin resistance. The results of this work expand our knowledge of the resistance profiles of vaginal LAB and provide evidence for the genetic basis of some acquired resistances. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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31 pages, 4988 KiB

Open AccessArticle

A Survey of Antimicrobial Resistance Determinants in Category A Select Agents, Exempt Strains, and Near-Neighbor Species

by Chris R. Taitt, Tomasz A. Leski, Amy Chen, Kimberly L. Berk, Robert W. Dorsey, Michael J. Gregory, Shanmuga Sozhamannan, Kenneth G. Frey, Diane L. Dutt and Gary J. Vora

Int. J. Mol. Sci. 2020, 21(5), 1669; https://doi.org/10.3390/ijms21051669 - 29 Feb 2020

Cited by 5 | Viewed by 3223

Abstract

A dramatic increase in global antimicrobial resistance (AMR) has been well documented. Of particular concern is the dearth of information regarding the spectrum and prevalence of AMR within Category A Select Agents. Here, we performed a survey of horizontally and vertically transferred AMR [...] Read more.

A dramatic increase in global antimicrobial resistance (AMR) has been well documented. Of particular concern is the dearth of information regarding the spectrum and prevalence of AMR within Category A Select Agents. Here, we performed a survey of horizontally and vertically transferred AMR determinants among Category A agents and their near neighbors. Microarrays provided broad spectrum screening of 127 Francisella spp., Yersinia spp., and Bacillus spp. strains for the presence/absence of 500+ AMR genes (or families of genes). Detecting a broad variety of AMR genes in each genus, microarray analysis also picked up the presence of an engineered plasmid in a Y. pestis strain. High resolution melt analysis (HRMA) was also used to assess the presence of quinolone resistance-associated mutations in 100 of these strains. Though HRMA was able to detect resistance-causing point mutations in B. anthracis strains, it was not capable of discriminating these point mutations from other nucleotide substitutions (e.g., arising from sequence differences in near neighbors). Though these technologies are well-established, to our knowledge, this is the largest survey of Category A agents and their near-neighbor species for genes covering multiple mechanisms of AMR. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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19 pages, 5111 KiB

Open AccessArticle

Label-Free Proteomic Analysis of Molecular Effects of 2-Methoxy-1,4-naphthoquinone on Penicillium italicum

by Meixia Guo, Xiaoyong Zhang, Meiying Li, Taotao Li, Xuewu Duan, Dandan Zhang, Lianmei Hu and Riming Huang

Int. J. Mol. Sci. 2019, 20(14), 3459; https://doi.org/10.3390/ijms20143459 - 14 Jul 2019

Cited by 24 | Viewed by 3302

Abstract

Penicillium italicum is the principal pathogen causing blue mold of citrus. Searching for novel antifungal agents is an important aspect of the post-harvest citrus industry because of the lack of higher effective and low toxic antifungal agents. Herein, the effects of 2-methoxy-1,4-naphthoquinone (MNQ) [...] Read more.

Penicillium italicum is the principal pathogen causing blue mold of citrus. Searching for novel antifungal agents is an important aspect of the post-harvest citrus industry because of the lack of higher effective and low toxic antifungal agents. Herein, the effects of 2-methoxy-1,4-naphthoquinone (MNQ) on P. italicum and its mechanism were carried out by a series of methods. MNQ had a significant anti-P. italicum effect with an MIC value of 5.0 µg/mL. The label-free protein profiling under different MNQ conditions identified a total of 3037 proteins in the control group and the treatment group. Among them, there were 129 differentially expressed proteins (DEPs, up-regulated > 2.0-fold or down-regulated < 0.5-fold, p < 0.05), 19 up-regulated proteins, 26 down-regulated proteins, and 67 proteins that were specific for the treatment group and another 17 proteins that were specific for the control group. Of these, 83 proteins were sub-categorized into 23 hierarchically-structured GO classifications. Most of the identified DEPs were involved in molecular function (47%), meanwhile 27% DEPs were involved in the cellular component and 26% DEPs were involved in the biological process. Twenty-eight proteins identified for differential metabolic pathways by KEGG were sub-categorized into 60 classifications. Functional characterization by GO and KEGG enrichment results suggests that the DEPs are mainly related to energy generation (mitochondrial carrier protein, glycoside hydrolase, acyl-CoA dehydrogenase, and ribulose-phosphate 3-epimerase), NADPH supply (enolase, pyruvate carboxylase), oxidative stress (catalase, glutathione synthetase), and pentose phosphate pathway (ribulose-phosphate 3-epimerase and xylulose 5-phosphate). Three of the down-regulated proteins selected randomly the nitro-reductase family protein, mono-oxygenase, and cytochrome P450 were verified using parallel reaction monitoring. These findings illustrated that MNQ may inhibit P. italicum by disrupting the metabolic processes, especially in energy metabolism and stimulus response that are both critical for the growth of the fungus. In conclusion, based on the molecular mechanisms, MNQ can be developed as a potential anti-fungi agent against P. italicum. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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Review

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30 pages, 1912 KiB

Open AccessReview

Mechanisms Protecting Acinetobacter baumannii against Multiple Stresses Triggered by the Host Immune Response, Antibiotics and Outside-Host Environment

by Soroosh Monem, Beata Furmanek-Blaszk, Adrianna Łupkowska, Dorota Kuczyńska-Wiśnik, Karolina Stojowska-Swędrzyńska and Ewa Laskowska

Int. J. Mol. Sci. 2020, 21(15), 5498; https://doi.org/10.3390/ijms21155498 - 31 Jul 2020

Cited by 47 | Viewed by 7249

Abstract

Acinetobacter baumannii is considered one of the most persistent pathogens responsible for nosocomial infections. Due to the emergence of multidrug resistant strains, as well as high morbidity and mortality caused by this pathogen, A. baumannii was placed on the World Health Organization (WHO) [...] Read more.

Acinetobacter baumannii is considered one of the most persistent pathogens responsible for nosocomial infections. Due to the emergence of multidrug resistant strains, as well as high morbidity and mortality caused by this pathogen, A. baumannii was placed on the World Health Organization (WHO) drug-resistant bacteria and antimicrobial resistance research priority list. This review summarizes current studies on mechanisms that protect A. baumannii against multiple stresses caused by the host immune response, outside host environment, and antibiotic treatment. We particularly focus on the ability of A. baumannii to survive long-term desiccation on abiotic surfaces and the population heterogeneity in A. baumannii biofilms. Insight into these protective mechanisms may provide clues for the development of new strategies to fight multidrug resistant strains of A. baumannii. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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22 pages, 1429 KiB

Open AccessReview

Molecular Mechanisms, Epidemiology, and Clinical Importance of β-Lactam Resistance in Enterobacteriaceae

by Giulia De Angelis, Paola Del Giacomo, Brunella Posteraro, Maurizio Sanguinetti and Mario Tumbarello

Int. J. Mol. Sci. 2020, 21(14), 5090; https://doi.org/10.3390/ijms21145090 - 18 Jul 2020

Cited by 85 | Viewed by 11313

Abstract

Despite being members of gut microbiota, Enterobacteriaceae are associated with many severe infections such as bloodstream infections. The β-lactam drugs have been the cornerstone of antibiotic therapy for such infections. However, the overuse of these antibiotics has contributed to select β-lactam-resistant Enterobacteriaceae isolates, [...] Read more.

Despite being members of gut microbiota, Enterobacteriaceae are associated with many severe infections such as bloodstream infections. The β-lactam drugs have been the cornerstone of antibiotic therapy for such infections. However, the overuse of these antibiotics has contributed to select β-lactam-resistant Enterobacteriaceae isolates, so that β-lactam resistance is nowadays a major concern worldwide. The production of enzymes that inactivate β-lactams, mainly extended-spectrum β-lactamases and carbapenemases, can confer multidrug resistance patterns that seriously compromise therapeutic options. Further, β-lactam resistance may result in increases in the drug toxicity, mortality, and healthcare costs associated with Enterobacteriaceae infections. Here, we summarize the updated evidence about the molecular mechanisms and epidemiology of β-lactamase-mediated β-lactam resistance in Enterobacteriaceae, and their potential impact on clinical outcomes of β-lactam-resistant Enterobacteriaceae infections. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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21 pages, 1189 KiB

Open AccessReview

Antimicrobial Resistance in Veterinary Medicine: An Overview

by Ernesto Palma, Bruno Tilocca and Paola Roncada

Int. J. Mol. Sci. 2020, 21(6), 1914; https://doi.org/10.3390/ijms21061914 - 11 Mar 2020

Cited by 158 | Viewed by 23884

Abstract

Antimicrobial resistance (AMR) represents one of the most important human- and animal health-threatening issues worldwide. Bacterial capability to face antimicrobial compounds is an ancient feature, enabling bacterial survival over time and the dynamic surrounding. Moreover, bacteria make use of their evolutionary machinery to [...] Read more.

Antimicrobial resistance (AMR) represents one of the most important human- and animal health-threatening issues worldwide. Bacterial capability to face antimicrobial compounds is an ancient feature, enabling bacterial survival over time and the dynamic surrounding. Moreover, bacteria make use of their evolutionary machinery to adapt to the selective pressure exerted by antibiotic treatments, resulting in reduced efficacy of the therapeutic intervention against human and animal infections. The mechanisms responsible for both innate and acquired AMR are thoroughly investigated. Commonly, AMR traits are included in mobilizable genetic elements enabling the homogeneous diffusion of the AMR traits pool between the ecosystems of diverse sectors, such as human medicine, veterinary medicine, and the environment. Thus, a coordinated multisectoral approach, such as One-Health, provides a detailed comprehensive picture of the AMR onset and diffusion. Following a general revision of the molecular mechanisms responsible for both innate and acquired AMR, the present manuscript focuses on reviewing the contribution of veterinary medicine to the overall issue of AMR. The main sources of AMR amenable to veterinary medicine are described, driving the attention towards the indissoluble cross-talk existing between the diverse ecosystems and sectors and their cumulative cooperation to this warning phenomenon. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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8 pages, 599 KiB

Open AccessReview

Bioinformatics Approaches to the Understanding of Molecular Mechanisms in Antimicrobial Resistance

by Pieter-Jan Van Camp, David B. Haslam and Aleksey Porollo

Int. J. Mol. Sci. 2020, 21(4), 1363; https://doi.org/10.3390/ijms21041363 - 18 Feb 2020

Cited by 40 | Viewed by 11372

Abstract

Antimicrobial resistance (AMR) is a major health concern worldwide. A better understanding of the underlying molecular mechanisms is needed. Advances in whole genome sequencing and other high-throughput unbiased instrumental technologies to study the molecular pathogenicity of infectious diseases enable the accumulation of large [...] Read more.

Antimicrobial resistance (AMR) is a major health concern worldwide. A better understanding of the underlying molecular mechanisms is needed. Advances in whole genome sequencing and other high-throughput unbiased instrumental technologies to study the molecular pathogenicity of infectious diseases enable the accumulation of large amounts of data that are amenable to bioinformatic analysis and the discovery of new signatures of AMR. In this work, we review representative methods published in the past five years to define major approaches developed to-date in the understanding of AMR mechanisms. Advantages and limitations for applications of these methods in clinical laboratory testing and basic research are discussed. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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15 pages, 890 KiB

Open AccessReview

Molecular Mechanisms of Bacterial Resistance to Metal and Metal Oxide Nanoparticles

by Nereyda Niño-Martínez, Marco Felipe Salas Orozco, Gabriel-Alejandro Martínez-Castañón, Fernando Torres Méndez and Facundo Ruiz

Int. J. Mol. Sci. 2019, 20(11), 2808; https://doi.org/10.3390/ijms20112808 - 8 Jun 2019

Cited by 211 | Viewed by 10384

Abstract

The increase in bacterial resistance to one or several antibiotics has become a global health problem. Recently, nanomaterials have become a tool against multidrug-resistant bacteria. The metal and metal oxide nanoparticles are one of the most studied nanomaterials against multidrug-resistant bacteria. Several in [...] Read more.

The increase in bacterial resistance to one or several antibiotics has become a global health problem. Recently, nanomaterials have become a tool against multidrug-resistant bacteria. The metal and metal oxide nanoparticles are one of the most studied nanomaterials against multidrug-resistant bacteria. Several in vitro studies report that metal nanoparticles have antimicrobial properties against a broad spectrum of bacterial species. However, until recently, the bacterial resistance mechanisms to the bactericidal action of the nanoparticles had not been investigated. Some of the recently reported resistance mechanisms include electrostatic repulsion, ion efflux pumps, expression of extracellular matrices, and the adaptation of biofilms and mutations. The objective of this review is to summarize the recent findings regarding the mechanisms used by bacteria to counteract the antimicrobial effects of nanoparticles. Full article

(This article belongs to the Special Issue Drug Resistance Mechanisms in Bacteria)

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