The Potential of Phage Therapy against the Emerging Opportunistic Pathogen Stenotrophomonas maltophilia

The isolation and characterization of bacteriophages for the treatment of infections caused by the multidrug resistant pathogen Stenotrophomonas maltophilia is imperative as nosocomial and community-acquired infections are rapidly increasing in prevalence. This increase is largely due to the numerous virulence factors and antimicrobial resistance genes encoded by this bacterium. Research on S. maltophilia phages to date has focused on the isolation and in vitro characterization of novel phages, often including genomic characterization, from the environment or by induction from bacterial strains. This review summarizes the clinical significance, virulence factors, and antimicrobial resistance mechanisms of S. maltophilia, as well as all phages isolated and characterized to date and strategies for their use. We further address the limited in vivo phage therapy studies conducted against this bacterium and discuss the future research needed to spearhead phages as an alternative treatment option against multidrug resistant S. maltophilia.

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Genomic analysis of multidrug-resistant clinical Enterococcus faecalis isolates for antimicrobial resistance genes and virulence factors from the western region of Saudi Arabia

Antimicrobial Resistance and Infection Control ◽

10.1186/s13756-019-0508-4 ◽

2019 ◽

Vol 8 (1) ◽

Cited By ~ 9

Author(s):

Muhammad Farman ◽

Muhammad Yasir ◽

Rashad R. Al-Hindi ◽

Suha A. Farraj ◽

Asif A. Jiman-Fatani ◽

...

Keyword(s):

Saudi Arabia ◽

Antimicrobial Resistance ◽

Enterococcus Faecalis ◽

Virulence Factors ◽

Resistance Genes ◽

Genomic Analysis ◽

Multidrug Resistant ◽

Western Region ◽

Antimicrobial Resistance Genes ◽

The Western Region

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Characterization of commensal Escherichia coli isolates from slaughtered sheep in Mexico

The Journal of Infection in Developing Countries ◽

10.3855/jidc.14001 ◽

2021 ◽

Vol 15 (11) ◽

pp. 1755-1760

Author(s):

Jorge Acosta-Dibarrat ◽

Edgar Enriquez-Gómez ◽

Martín Talavera-Rojas ◽

Edgardo Soriano-Vargas ◽

Armando Navarro ◽

...

Keyword(s):

Escherichia Coli ◽

Antimicrobial Resistance ◽

Multidrug Resistant ◽

Phylogenetic Group ◽

Phylogenetic Groups ◽

E Coli ◽

New Information ◽

Antimicrobial Resistance Genes ◽

Uremic Syndrome

Introduction: Commensal Escherichia coli is defined as bacteria without known virulence factors that could be playing a specific role in some diseases; however, they could be responsible to disseminate antimicrobial resistance genes to other microorganisms. This study aimed to characterize the commensal E. coli isolates obtained from slaughtered sheep in the central region of Mexico. Methodology: Isolates were classified as commensal E. coli when distinctive genes related to diarrheagenic pathotypes (stx1, stx2, eae, bfp, LT, stp, ipaH, and aggR) were discarded by PCR. Identification of serotype, phylogenetic group, and antimicrobial resistance was also performed. Results: A total of 41 isolates were characterized. The phylogenetic groups found were B1 in 37 isolates (90.2%), A in 2 (4.8%), and 1 isolate (2.4%) for C and D groups. Serotypes associated with diarrhea in humans (O104:H2 and O154:NM) and hemolytic uremic syndrome (O8:NM) were detected. Thirty-three isolates (80%) were resistant to ceftazidime, 23 (56%), to tetracycline 8 (19.5%) to ampicillin, and 1 to amikacin. Six isolates (14.6%) were multidrug-resistant. Conclusions: This study provides new information about commensal E. coli in slaughtered sheep, high percentages of resistance to antibiotics, and different profiles of antimicrobial resistance were found, their dissemination constitute a risk factor towards the consuming population.

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Characterization of Acquired Antimicrobial Resistance Genes in Environmental Stenotrophomonas maltophilia Isolates from Brazil

Microbial Drug Resistance ◽

10.1089/mdr.2018.0216 ◽

2019 ◽

Vol 25 (4) ◽

pp. 475-479 ◽

Cited By ~ 4

Author(s):

João Pedro Rueda Furlan ◽

Danilo Garcia Sanchez ◽

Inara Fernanda Lage Gallo ◽

Eliana Guedes Stehling

Keyword(s):

Antimicrobial Resistance ◽

Resistance Genes ◽

Stenotrophomonas Maltophilia ◽

Antimicrobial Resistance Genes

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Characteristics of High-Level Aminoglycoside-Resistant Enterococcus faecalis Isolated from Bulk Tank Milk in Korea

Animals ◽

10.3390/ani11061724 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1724

Author(s):

Hyo Jung Kang ◽

Sunghyun Yoon ◽

Koeun Kim ◽

Young Ju Lee

Keyword(s):

Antimicrobial Resistance ◽

Enterococcus Faecalis ◽

Virulence Factors ◽

Virulence Genes ◽

Multidrug Resistant ◽

Management Program ◽

Bulk Tank Milk ◽

Antimicrobial Resistance Genes ◽

Bulk Tank ◽

High Level

Enterococci, which are considered environmental mastitis-causing pathogens, have easily acquired aminoglycoside-resistant genes that encode various aminoglycoside-modifying enzymes (AME). Therefore, this study was conducted to compare the distribution of high-level aminoglycoside-resistant (HLAR) and multidrug-resistant (MDR) Enterococcus faecalis (E. faecalis) bacteria isolated from bulk tank milk in four dairy companies in Korea. Moreover, it analyzed the characteristics of their antimicrobial resistance genes and virulence factors. Among the 301 E. faecalis bacteria studied, 185 (61.5%) showed HLAR with no significant differences among the dairy companies. Furthermore, 129 (69.7%) of the 185 HLAR E. faecalis showed MDR without significant differences among companies. In contrast, HLAR E. faecalis from companies A, B, and C were significantly higher in resistance to the four classes than those in company D, which had the highest MDR ability against the three antimicrobial classes (p < 0.05). In addition, in the distribution of AME genes, 72 (38.9%) and 36 (19.5%) of the isolates carried both aac(6′)Ie-aph(2″)-la and ant(6)-Ia genes, and the ant (6)-Ia gene alone, respectively, with significant differences among the companies (p < 0.05). In the distribution of virulence genes, the ace (99.5%), efa A (98.9%), and cad 1 (98.4%) genes were significantly prevalent (p < 0.05). Thus, our results support that an advanced management program by companies is required to minimize the dissemination of antimicrobial resistance and virulence factors.

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Genomic Investigation of Antimicrobial-Resistant Salmonella enterica Isolates From Dead Chick Embryos in China

Frontiers in Microbiology ◽

10.3389/fmicb.2021.684400 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mohammed Elbediwi ◽

Yanting Tang ◽

Dawei Shi ◽

Hazem Ramadan ◽

Yaohui Xu ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Chick Embryo ◽

Virulence Factors ◽

Resistance Genes ◽

Salmonella Enterica ◽

Multidrug Resistant ◽

Henan Province ◽

Health Concern ◽

Antimicrobial Resistance Genes ◽

Genomic Characterization

Salmonella spp. is recognized as an important zoonotic pathogen. The emergence of antimicrobial resistance in Salmonella enterica poses a great public health concern worldwide. While the knowledge on the incidence and the characterization of different S. enterica serovars causing chick embryo death remains obscure in China. In this study, we obtained 45 S. enterica isolates from 2,139 dead chick embryo samples collected from 28 breeding chicken hatcheries in Henan province. The antimicrobial susceptibility assay was performed by the broth microdilution method and the results showed that 31/45 (68.8%) isolates were multidrug-resistant (≥3 antimicrobial classes). Besides the highest resistance rate was observed in the aminoglycoside class, all the isolates were susceptible to chloramphenicol, azithromycin, and imipenem. Furthermore, genomic characterization revealed that S. Enteritidis (33.33%; 15/45) was a frequent serovar that harbored a higher number of virulence factors compared to other serovars. Importantly, genes encoding β-lactamases were identified in three serovars (Thompson, Enteritidis, and Kottbus), whereas plasmid-mediated quinolone resistance genes (qnrB4) were detected in certain isolates of S. Thompson and the two S. Kottbus isolates. All the examined isolates harbored the typical virulence factors from Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2). Additionally, a correlation analysis between the antimicrobial resistance genes, phenotype, and plasmids was conducted among Salmonella isolates. It showed strong positive correlations (r < 0.6) between the different antimicrobial-resistant genes belonging to certain antimicrobial classes. Besides, IncF plasmid showed a strong negative correlation (r > −0.6) with IncHI2 and IncHI2A plasmids. Together, our study demonstrated antimicrobial-resistant S. enterica circulating in breeding chicken hatcheries in Henan province, highlighting the advanced approach, by using genomic characterization and statistical analysis, in conducting the routine monitoring of the emerging antimicrobial-resistant pathogens. Our findings also proposed that the day-old breeder chicks trading could be one of the potential pathways for the dissemination of multidrug-resistant S. enterica serovars.

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BKC-2, a New BKC Variant Detected in MCR-9.1-producing Enterobacter hormaechei subsp. xiangfangensis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01193-20 ◽

2020 ◽

pp. AAC.01193-20

Author(s):

Willames M. B. S. Martins ◽

Evelin R. Martins ◽

Letícia K. de Andrade ◽

Refath Farzana ◽

Timothy R. Walsh ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Resistance Gene ◽

Resistance Genes ◽

Tertiary Hospital ◽

Multidrug Resistant ◽

Colistin Resistance ◽

Antimicrobial Resistance Genes ◽

Genomic Characterization ◽

Enterobacter Hormaechei

We performed the characterization of a multidrug-resistant (MDR) Enterobacter spp. isolate highlighting the genetic aspects of the antimicrobial resistance genes. An Enterobacter spp. isolate (Ec61) was recovered in 2014 from a transtracheal aspirate sample from a patient admitted to a Brazilian tertiary hospital and submitted to further microbiological and genomic characterization. Ec61 was identified as Enterobacter hormaechei subsp. xiangfangensis ST451, showed a MDR profile and the presence of genes codifying new β-lactamase variants, BKC-2 and ACT-84, and the mobile colistin resistance gene mcr-9.1.

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Phenotypic and genotypic characterization of mcr-1-positive multidrug-resistant Escherichia coli ST93, ST117, ST156, ST10, and ST744 isolated from poultry in Poland

Brazilian Journal of Microbiology ◽

10.1007/s42770-021-00538-8 ◽

2021 ◽

Author(s):

Katarzyna Ćwiek ◽

Anna Woźniak-Biel ◽

Magdalena Karwańska ◽

Magdalena Siedlecka ◽

Christine Lammens ◽

...

Keyword(s):

Escherichia Coli ◽

Antimicrobial Resistance ◽

Resistance Genes ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Genetic Relatedness ◽

Multidrug Resistant ◽

E Coli ◽

Antimicrobial Resistance Genes

Abstract Background A plasmid-mediated mechanism of bacterial resistance to polymyxin is a serious threat to public health worldwide. The present study aimed to determine the occurrence of plasmid-mediated colistin resistance genes and to conduct the molecular characterization of mcr-positive Escherichia coli strains isolated from Polish poultry. Methods In this study, 318 E. coli strains were characterized by the prevalence of mcr1–mcr5 genes, antimicrobial susceptibility testing by minimal inhibitory concentration method, the presence of antimicrobial resistance genes was screened by PCR, and the biofilm formation ability was tested using the crystal violet staining method. Genetic relatedness of mcr-1-positive E. coli strains was evaluated by multilocus sequence typing method. Results Among the 318 E. coli isolates, 17 (5.35%) harbored the mcr-1 gene. High antimicrobial resistance rates were observed for ampicillin (100%), tetracycline (88.24%), and chloramphenicol (82.35%). All mcr-1-positive E. coli strains were multidrug-resistant, and as many as 88.24% of the isolates contained the blaTEM gene, tetracycline (tetA and tetB), and sulfonamide (sul1, sul2, and sul3) resistance genes. Additionally, 41.18% of multidrug-resistant, mcr-1-positive E. coli isolates were moderate biofilm producers, while the rest of the strains showed weak biofilm production. Nine different sequence types were identified, and the dominant ST was ST93 (29.41%), followed by ST117 (17.65%), ST156 (11.76%), ST 8979 (11.76%), ST744 (5.88%), and ST10 (5.88%). Moreover, the new ST was identified in this study. Conclusions Our results showed a low occurrence of mcr-1-positive E. coli strains isolated from Polish poultry; however, all the isolated strains were resistant to multiple antimicrobial agents and were able to form biofilms at low or medium level.

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Isolation and characterization of Pseudomonas aeruginosa bacteriophages — potential agents for phage therapy

10.47183/mes.2021.027 ◽

2021 ◽

Author(s):

MA Kornienko ◽

NS Kuptsov ◽

DI Danilov ◽

RB Gorodnichev ◽

MV Malakhova ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Phage Therapy ◽

Illumina Miseq ◽

Multidrug Resistant ◽

Open Reading Frames ◽

Lytic Activity ◽

Isolation And Characterization ◽

Double Stranded Dna ◽

Activity Spectrum

Pseudomonas aeruginosa — is one of the pathogens characterized by the critical number of multidrug-resistant (MDR) strains. Phage therapy is considered an alternative to antibiotics, especially in treatment of infections caused by MDR strains. The aim of this study was to isolate and characterize P. aeruginosa phages that could potentially be suitable for treating infectious diseases. To isolate the P. aeruginosa phages, enrichment cultures were used. The lytic activity spectrum was confirmed by spot testing on 40 P. aeruginosa strains. Whole-genome sequencing was performed using Illumina MiSeq instrument. Phylogenetic analysis was done using VICTOR tool. Isolated phages vB_PaeA-55-1w and vB_PaeM-198 from Autographiviridae and Myoviridae families, respectively, had a broad spectrum of lytic activity (about 50% each), including lysis of MDR strains. The genomes vB_PaeA-55-1w and vB_PaeM-198 comprise double-stranded DNA of 42.5 and 66.3 kbp in length, respectively. Open reading frames were annotated for both phages (52 for vB_PaeA-55-1w, and 95 for vB_PaeM-198), no integrases and toxins were detected. On a phylogenetic tree, vB_PaeA-55-1w phage was clustered with phages from the Phikmvvirus genus (Autographiviridae family), which are also used in phage therapy. vB_PaeM-198 phage was clustered with phages from the Pbunavirus genus (Myoviridae family). vB_PaeA-55-1w and vB_PaeM-198 phages could be considered as candidates for phage therapy and may be used to treat infections caused by MDR P. aeruginosa.

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Isolation and Characterization of the Novel Bacteriophage AXL3 against Stenotrophomonas maltophilia

International Journal of Molecular Sciences ◽

10.3390/ijms21176338 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6338

Author(s):

Jaclyn G. McCutcheon ◽

Andrea Lin ◽

Jonathan J. Dennis

Keyword(s):

Host Range ◽

Stenotrophomonas Maltophilia ◽

Phage Therapy ◽

Bacterial Pathogen ◽

Future Research ◽

The Novel ◽

Range Analysis ◽

Virulent Phage ◽

Isolation And Characterization ◽

Successful Infection

The rapid increase in the number of worldwide human infections caused by the extremely antibiotic resistant bacterial pathogen Stenotrophomonas maltophilia is cause for concern. An alternative treatment solution in the post-antibiotic era is phage therapy, the use of bacteriophages to selectively kill bacterial pathogens. In this study, the novel bacteriophage AXL3 (vB_SmaS-AXL_3) was isolated from soil and characterized. Host range analysis using a panel of 29 clinical S. maltophilia isolates shows successful infection of five isolates and electron microscopy indicates that AXL3 is a member of the Siphoviridae family. Complete genome sequencing and analysis reveals a 47.5 kb genome predicted to encode 65 proteins. Functionality testing suggests AXL3 is a virulent phage and results show that AXL3 uses the type IV pilus, a virulence factor on the cell surface, as its receptor across its host range. This research identifies a novel virulent phage and characterization suggests that AXL3 is a promising phage therapy candidate, with future research examining modification through genetic engineering to broaden its host range.

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