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Antimicrobial Resistance—New Insights 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 17532

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Dr. Cidália Pina-Vaz

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1. Department of Microbiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
2. CINTESIS, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
Interests: antimicrobial susceptibility assays; microbial mechanisms of resistance; flow cytometry and microbiology; rapid antimicrobial susceptibility assays
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Special Issue Information

Dear Colleagues,

Health care has been a hot topic recently. Before the COVID-19 pandemic, antimicrobial resistance was already a major global concern. During—and certainly after—the pandemic, this topic will continue to be a cause of global concern and an urgent topic requiring research efforts. Infectious disease treatment requires disruptive strategies, including new drugs, knowledge about mechanisms of resistance, and faster diagnostic tests. New drugs are necessary, entailing the development of new molecules and the search for alternative microbe targets. Molecular knowledge of the underlying mechanisms of resistance would help to eventually revert resistance and recover some old molecules. Additionally, but no less important, is the development of rapid solutions from microbiology labs in order to guide antimicrobial therapy, avoiding broad-spectrum empiric treatment. To help antimicrobial stewardship, the development of antimicrobial dosing for some drugs and in special patients is also required.

Dr. Cidália Pina-Vaz
Guest Editor

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Keywords

antimicrobial resistance
mechanisms of antimicrobial resistance
rapid antimicrobial susceptible assays
antimicrobial dosing
molecular assays

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Published Papers (9 papers)

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Research

13 pages, 2770 KiB

Open AccessArticle

Beetroot (Beta vulgaris) Extract against Salmonella Typhimurium via Apoptosis-Like Death and Its Potential for Application in Cooked Pork

by Shaoying Gong, Chaoqin Jiao, Ling Guo and Yujun Jiang

Int. J. Mol. Sci. 2023, 24(18), 14217; https://doi.org/10.3390/ijms241814217 - 18 Sep 2023

Cited by 2 | Viewed by 1294

Abstract

Salmonella Typhimurium is a common foodborne pathogen in meat and meat products, causing significant harm and losses to producers and consumers. The aim of this study was to investigate the antibacterial activity and possible mechanisms of beetroot (Beta vulgaris) extract against S. Typhimurium, as well as the application potential in cooked pork. The results suggested beetroot extract could inhibit S. Typhimurium with a minimum inhibitory concentration (MIC) of 20 mg/mL. After treatment with beetroot extract (1 or 2 MIC), S. Typhimurium exhibited the characteristics of apoptotic-like death (ALD), such as membrane depolarization, phosphatidylserine (PS) externalization, caspase-like protein activation, and DNA fragmentation. Further research has shown that the ALD induced by beetroot extract in S. Typhimurium was caused by reactive oxygen species (ROS) consumption, which was different from most natural products. The treatment of cooked pork with beetroot extract could reduce the number of S. Typhimurium, lower pH, defer lipid oxidation, and improve the colour. These results indicate that beetroot extract can inhibit S. Typhimurium through the ALD mechanism and has potential as an antibacterial agent against S. Typhimurium in ready-to-eat meat products. Full article

(This article belongs to the Special Issue Antimicrobial Resistance—New Insights 2.0)

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13 pages, 1218 KiB

Open AccessArticle

Isolation, Identification and Antimicrobial Resistance Analysis of Canine Oral and Intestinal Escherichia coli Resistant to Colistin

by Hui-Hua Zheng, Chao Yu, Xin-Yue Tang, Chong-Tao Du and Guang-Hong Xie

Int. J. Mol. Sci. 2023, 24(17), 13428; https://doi.org/10.3390/ijms241713428 - 30 Aug 2023

Viewed by 1502

Abstract

In recent years, the antimicrobial resistance in Escherichia coli has gradually developed into a global problem. These resistant bacteria could be transmitted to humans through animal feces in the environment or direct contact with pets, leading to a problem in bacterial treatment for humans and animals. Now, the antibiotic resistance of oral and intestinal microbiota from dog origins remains unclear in China. Therefore, this study first analyzed the current colistin resistance of oral and intestinal microbiota from dog origins in mainland China. A total of 536 samples were collected from dogs in mainland China and, respectively, cultured on the SS and MacConkey agar plate containing colistin (4 μg/mL) to obtain bacteria, and the antibiotic-resistance phenotype of Escherichia coli was investigated for nine antibiotics. Results showed that a total of 2259 colistin-resistant bacteria were isolated from samples and identified, and among them, the isolated rate of Escherichia coli (34.01%, 769/2259) was relatively higher than that of other bacteria. Subsequently, it was found that the resistance of these Escherichia coli was very severe by exploring its resistance to different antibiotics, particularly to three common antibiotics in a clinic which were ceftriaxone, ampicillin and trimethoprim/sulfamethoxazole, with the resistance rates of 60.60% (466/769), 57.22% (440/769), and 53.06% (408/769), respectively. Moreover, the simultaneous resistance of Escherichia coli to one or more antibiotics was determined, and 69.96% (538/769) strains have defined the resistance to both two or more antibiotics, and even 13 of Escherichia coli strains that were resistant to all nine antibiotics, indicating that the Escherichia coli from dog origins has severe antibiotic resistance in the clinic. In conclusion, this study guided the use of antibiotics and could draw attention to antibiotic resistance in veterinary clinical treatment for animals in the future. Full article

(This article belongs to the Special Issue Antimicrobial Resistance—New Insights 2.0)

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26 pages, 15168 KiB

Open AccessArticle

Phage Targeting Neonatal Meningitis E. coli K1 In Vitro in the Intestinal Microbiota of Pregnant Donors and Impact on Bacterial Populations

by Céline Antoine, Fanny Laforêt, Elizabeth Goya-Jorge, Irma Gonza, Sarah Lebrun, Caroline Douny, Jean-Noël Duprez, Abdoulaye Fall, Bernard Taminiau, Marie-Louise Scippo, Georges Daube, Damien Thiry and Véronique Delcenserie

Int. J. Mol. Sci. 2023, 24(13), 10580; https://doi.org/10.3390/ijms241310580 - 24 Jun 2023

Cited by 4 | Viewed by 1791

Abstract

Escherichia coli K1 is a leading cause of neonatal meningitis. The asymptomatic carriage of these strains in the maternal intestinal microbiota constitutes a risk of vertical transmission to the infant at birth. The aim of this work was to evaluate the efficacy of phage therapy against E. coli K1 in an intestinal environment and its impact on the intestinal microbiota. For this purpose, three independent experiments were conducted on the SHIME® system, the first one with only the phage vB_EcoP_K1_ULINTec4, the second experiment with only E. coli K1 and the last experiment with both E. coli K1 and the phage. Microbiota monitoring was performed using metagenetics, qPCR, SCFA analysis and the induction of AhR. The results showed that phage vB_EcoP_K1_ULINTec4, inoculated alone, was progressively cleared by the system and replicates in the presence of its host. E. coli K1 persisted in the microbiota but decreased in the presence of the phage. The impact on the microbiota was revealed to be donor dependent, and the bacterial populations were not dramatically affected by vB_K1_ULINTec4, either alone or with its host. In conclusion, these experiments showed that the phage was able to infect the E. coli K1 in the system but did not completely eliminate the bacterial load. Full article

(This article belongs to the Special Issue Antimicrobial Resistance—New Insights 2.0)

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11 pages, 990 KiB

Open AccessArticle

Genomic Characterization of Uropathogenic Escherichia coli Isolates from Tertiary Hospitals in Riyadh, Saudi Arabia

by Rawan H. Aljohani, Dalia S. ElFeky, Abdulrahman A. Alswaji, Eisa Alrashidi, Liliane Okdah, Bassam Alalwan, Sameera M. Aljohani, Hanan H. Balkhy, Alya Redhwan and Majed F. Alghoribi

Int. J. Mol. Sci. 2023, 24(8), 7582; https://doi.org/10.3390/ijms24087582 - 20 Apr 2023

Cited by 3 | Viewed by 1875

Abstract

Uropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract infections (UTIs) in hospitalised and non-hospitalised patients. Genomic analysis was used to gain further insight into the molecular characteristics of UPEC isolates from Saudi Arabia. A total of 165 isolates were collected from patients with UTIs between May 2019 and September 2020 from two tertiary hospitals in Riyadh, Saudi Arabia. Identification and antimicrobial susceptibility testing (AST) were performed using the VITEK system. Extended-spectrum β-lactamase (ESBL)-producing isolates (n = 48) were selected for whole genome sequencing (WGS) analysis. In silico analysis revealed that the most common sequence types detected were ST131 (39.6%), ST1193 (12.5%), ST73 (10.4%), and ST10 (8.3%). Our finding showed that bla_CTX-M-15 gene was detected in the majority of ESBL isolates (79.2%), followed by bla_CTX-M-27 (12.5%) and bla_CTX-M-8 (2.1%). ST131 carried bla_CTX-M-15 or bla_CTX-M-27, and all ST73 and ST1193 carried bla_CTX-M-15. The relatively high proportion of ST1193 in this study was notable as a newly emerged lineage in the region, which warrants further monitoring. Full article

(This article belongs to the Special Issue Antimicrobial Resistance—New Insights 2.0)

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13 pages, 5288 KiB

Open AccessArticle

A Novel Hybrid Platform for Live/Dead Bacteria Accurate Sorting by On-Chip DEP Device

by Annarita di Toma, Giuseppe Brunetti, Maria Serena Chiriacò, Francesco Ferrara and Caterina Ciminelli

Int. J. Mol. Sci. 2023, 24(8), 7077; https://doi.org/10.3390/ijms24087077 - 11 Apr 2023

Cited by 10 | Viewed by 1894

Abstract

According to the World Health Organization (WHO) forecasts, Antimicrobial Resistance (AMR) will be the leading cause of death worldwide in the next decades. To prevent this phenomenon, rapid Antimicrobial Susceptibility Testing (AST) techniques are required to drive the selection of the most suitable antibiotic and its dosage. In this context, we propose an on-chip platform, based on a micromixer and a microfluidic channel, combined with a pattern of engineered electrodes to exploit the di-electrophoresis (DEP) effect. The role of the micromixer is to ensure the proper interaction of the antibiotic with the bacteria over a long time (≈1 h), and the DEP-based microfluidic channel enables the efficient sorting of live from dead bacteria. A sorting efficiency of more than 98%, with low power consumption (V_pp = 1 V) and time response of 5 s, within a chip footprint of ≈86 mm², has been calculated, which makes the proposed system very attractive and innovative for efficient and rapid monitoring of the antimicrobial susceptibility at the single-bacterium level in next-generation medicine. Full article

(This article belongs to the Special Issue Antimicrobial Resistance—New Insights 2.0)

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15 pages, 1828 KiB

Open AccessArticle

Collateral Sensitivity to Fosfomycin of Tobramycin-Resistant Mutants of Pseudomonas aeruginosa Is Contingent on Bacterial Genomic Background

by Roberta Genova, Pablo Laborda, Trinidad Cuesta, José Luis Martínez and Fernando Sanz-García

Int. J. Mol. Sci. 2023, 24(8), 6892; https://doi.org/10.3390/ijms24086892 - 7 Apr 2023

Cited by 2 | Viewed by 2195

Abstract

Understanding the consequences in bacterial physiology of the acquisition of drug resistance is needed to identify and exploit the weaknesses derived from it. One of them is collateral sensitivity, a potentially exploitable phenotype that, unfortunately, is not always conserved among different isolates. The identification of robust, conserved collateral sensitivity patterns is then relevant for the translation of this knowledge into clinical practice. We have previously identified a robust fosfomycin collateral sensitivity pattern of Pseudomonas aeruginosa that emerged in different tobramycin-resistant clones. To go one step further, here, we studied if the acquisition of resistance to tobramycin is associated with robust collateral sensitivity to fosfomycin among P. aeruginosa isolates. To that aim, we analyzed, using adaptive laboratory evolution approaches, 23 different clinical isolates of P. aeruginosa presenting diverse mutational resistomes. Nine of them showed collateral sensitivity to fosfomycin, indicating that this phenotype is contingent on the genetic background. Interestingly, collateral sensitivity to fosfomycin was linked to a larger increase in tobramycin minimal inhibitory concentration. Further, we unveiled that fosA low expression, rendering a higher intracellular accumulation of fosfomycin, and a reduction in the expression of the P. aeruginosa alternative peptidoglycan-recycling pathway enzymes, might be on the basis of the collateral sensitivity phenotype. Full article

(This article belongs to the Special Issue Antimicrobial Resistance—New Insights 2.0)

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18 pages, 2827 KiB

Open AccessArticle

Identification of a Small Molecule Compound Active against Antibiotic-Tolerant Staphylococcus aureus by Boosting ATP Synthesis

by Ho-Ting-Venice Iu, Pak-Ming Fong, Hin-Cheung-Bill Yam, Peng Gao, Bingpeng Yan, Pok-Man Lai, Victor-Yat-Man Tang, Ka-Ho Li, Chi-Wang Ma, King-Hei-Kenneth Ng, Kong-Hung Sze, Dan Yang, Julian Davies and Richard-Yi-Tsun Kao

Int. J. Mol. Sci. 2023, 24(7), 6242; https://doi.org/10.3390/ijms24076242 - 26 Mar 2023

Cited by 1 | Viewed by 2453

Abstract

Antibiotic tolerance poses a threat to current antimicrobial armamentarium. Bacteria at a tolerant state survive in the presence of antibiotic treatment and account for persistence, relapse and recalcitrance of infections. Antibiotic treatment failure may occur due to antibiotic tolerance. Persistent infections are difficult to treat and are often associated with poor prognosis, imposing an enormous burden on the healthcare system. Effective strategies targeting antibiotic-tolerant bacteria are therefore highly warranted. In this study, small molecule compound SA-558 was identified to be effective against Staphylococcus aureus that are tolerant to being killed by conventional antibiotics. SA-558 mediated electroneutral transport across the membrane and led to increased ATP and ROS generation, resulting in a reduction of the population of antibiotic-tolerant bacteria. In a murine chronic infection model, of which vancomycin treatment failed, we demonstrated that SA-558 alone and in combination with vancomycin caused significant reduction of MRSA abundance. Our results indicate that SA-558 monotherapy or combinatorial therapy with vancomycin is an option for managing persistent S. aureus bacteremia infection and corroborate that bacterial metabolism is an important target for counteracting antibiotic tolerance. Full article

(This article belongs to the Special Issue Antimicrobial Resistance—New Insights 2.0)

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13 pages, 1823 KiB

Open AccessArticle

Clonal Spreading of ST42 Staphylococcus haemolyticus Strains Occurs Possibly Due to fusB and tetK Resistant Genes and Capsule-Related Genes

by Lee-Chung Lin, Shih-Cheng Chang, Yu-Hsiang Ou, Tsui-Ping Liu and Jang-Jih Lu

Int. J. Mol. Sci. 2023, 24(7), 6198; https://doi.org/10.3390/ijms24076198 - 24 Mar 2023

Cited by 1 | Viewed by 1532

Abstract

Multi-drug resistant Staphylococcus haemolyticus is a frequent nosocomial invasive bacteremia pathogen in hospitals. Our previous analysis showed one of the predominant strains, ST42 originated from ST3, had only one multilocus sequence typing (MLST) variation among seven loci in SH1431; yet no significant differences in biofilm formation observed between ST42 and ST3, suggesting that other factors influence clonal lineage change. Whole genome sequencing was conducted on two isolates from ST42 and ST3 to find phenotypic and genotypic variations, and these variations were further validated in 140 clinical isolates. The fusidic acid- and tetracycline-resistant genes (fusB and tetK) were found only in CGMH-SH51 (ST42). Further investigation revealed consistent resistant genotypes in all isolates, with 46% and 70% of ST42 containing fusB and tetK, respectively. In contrast, only 23% and 4.2% ST3 contained these two genes, respectively. The phenotypic analysis also showed that ST42 isolates were highly resistant to fusidic acid (47%) and tetracycline (70%), compared with ST3 (23% and 4%, respectively). Along with drug-resistant genes, three capsule-related genes were found in higher percentage distributions in ST42 than in ST3 isolates. Our findings indicate that ST42 could become endemic in Taiwan, further constitutive surveillance is required to prevent the spread of this bacterium. Full article

(This article belongs to the Special Issue Antimicrobial Resistance—New Insights 2.0)

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15 pages, 605 KiB

Open AccessArticle

Novel Antibiotic Resistance Genes Identified by Functional Gene Library Screening in Stenotrophomonas maltophilia and Chryseobacterium spp. Bacteria of Soil Origin

by Laurita Klimkaitė, Ignas Ragaišis, Renatas Krasauskas, Modestas Ružauskas, Edita Sužiedėlienė and Julija Armalytė

Int. J. Mol. Sci. 2023, 24(7), 6037; https://doi.org/10.3390/ijms24076037 - 23 Mar 2023

Cited by 4 | Viewed by 2137

Abstract

As one of the most diverse habitats of microorganisms, soil has been recognised as a reservoir of both antibiotics and the antibiotic resistance genes (ARGs). Bacteria naturally inhabiting soil or water often possess innate ARGs to counteract the chemical compounds produced by competitors living in the same environment. When such bacteria are able to cause infections in immunocompromised patients, their strong innate antibiotic resistance mechanisms make treatment difficult. We generated functional gene libraries using antibiotic-resistant Stenotrophomonas maltophilia and Chryseobacterium spp. bacteria isolated from agricultural soils in Lithuania to select for the genetic determinants responsible for their resistance. We were able to find novel variants of aminoglycoside and β-lactam resistance genes, with β-lactamases isolated from the Chryseobacterium spp. functional gene library, one of which is a variant of IND-like metallo-β-lactamase (MBL) IND-17 and the other of which is a previously uncharacterised MBL we named CHM (Chryseobacterium metallo β-lactamase). Our results indicate that soil microorganisms possess a diversity of ARG variants, which could potentially be transferred to the clinical setting. Full article

(This article belongs to the Special Issue Antimicrobial Resistance—New Insights 2.0)

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