Isolation and Characterization of Novel Lytic Phages Infecting Multidrug-Resistant Escherichia coli

被引:21
作者
Vera-Mansilla, Javiera [1 ]
Sanchez, Patricio [1 ]
Silva-Valenzuela, Cecilia A. [1 ]
Molina-Quiroz, Roberto C. [1 ]
机构
[1] Ctr Estudios Cient, Valdivia, Chile
关键词
Escherichia coli; antibiotic resistance; multidrug-resistant clinical isolates; bacteriophages; urinary tract infections; antibiotic-resistant pathogens; LPS; phage-host interactions; phage predation; lipopolysaccharide; URINARY-TRACT-INFECTIONS; O-ANTIGEN; PROTEIN; SEQUENCE; DATABASE; CORE; BACTERIOPHAGES; EPIDEMIOLOGY; PHYLOGENIES; MECHANISMS;
D O I
10.1128/spectrum.01678-21
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Urinary tract infections (UTIs) are the second most frequent bacterial infections worldwide, with Escherichia coli being the main causative agent. The increase of antibiotic-resistance determinants among isolates from clinical samples, including UTIs, makes the development of novel therapeutic strategies a necessity. In this context, the use of bacteriophages as a therapeutic alternative has been proposed, due to their ability to efficiently kill bacteria. In this work, we isolated and characterized three novel bacteriophages, microbes laboratory phage 1 (MLP1), MLP2, and MLP3, belonging to the Chaseviddae, Myoviridae, and Podoviridae families, respectively. These phages efficiently infect and kill laboratory reference strains and multidrug-resistant clinical E. coli isolates from patients with diagnosed UTIs. Interestingly, these phages are also able to infect intestinal pathogenic Escherichia coli strains, such as enteroaggregative E. coli and diffusely adherent E. coli. Our data show that the MLP phages recognize different regions of the lipopolysaccharide (LPS) molecule, an important virulence factor in bacteria that is also highly variable among different E. coli strains. Altogether, our results suggest that these phages may represent an interesting alternative for the treatment of antibiotic-resistant E. coli. IMPORTANCE Urinary tract infections affect approximately 150 million people annually. The current antibiotic resistance crisis demands the development of novel therapeutic alternatives. Our results show that three novel phages, MLP1, MLP2, and MLP3 are able to infect both laboratory and multidrug-resistant clinical isolates of Escherichia colt. Since these phages (i) efficiently kill antibiotic-resistant clinical isolates of uropathogenic Escherichia coli (UPEC), (ii) recognize different portions of the LPS molecule, and (iii) are able to efficiently infect intestinal pathogenic Escherichia coli hosts, we believe that these novel phages are good candidates to be used as a therapeutic alternative to treat antibiotic-resistant E. coli strains generating urinary tract and/or intestinal infections.
引用
收藏
页数:15
相关论文
共 82 条
[21]   Phage Therapy-History from Twort and d'Herelle Through Soviet Experience to Current Approaches [J].
Chanishvili, Nina .
ADVANCES IN VIRUS RESEARCH, VOL 83: BACTERIOPHAGES, PT B, 2012, 83 :3-40
[22]   The characteristics and genome analysis of vB_ApiP_XC38, a novel phage infecting Acinetobacter pittii [J].
Cheng, Mengjun ;
Luo, Man ;
Xi, Hengyu ;
Zhao, Yunze ;
Le, Shuai ;
Chen, Li-Kuang ;
Tan, Demeng ;
Guan, Yuan ;
Wang, Tianqi ;
Han, Wenyu ;
Wu, Nannan ;
Zhu, Tongyu ;
Gu, Jingmin .
VIRUS GENES, 2020, 56 (04) :498-507
[23]   Rapid and precise alignment of raw reads against redundant databases with KMA [J].
Clausen, Philip T. L. C. ;
Aarestrup, Frank M. ;
Lund, Ole .
BMC BIOINFORMATICS, 2018, 19
[24]   Sequence of the Escherichia coli O26O antigen gene cluster and identification of O26 specific genes [J].
D'Souza, JA ;
Wang, L ;
Reeves, P .
GENE, 2002, 297 (1-2) :123-127
[25]   The Gut Microbiota Facilitates Drifts in the Genetic Diversity and Infectivity of Bacterial Viruses [J].
De Sordi, Luisa ;
Khanna, Varun ;
Debarbieux, Laurent .
CELL HOST & MICROBE, 2017, 22 (06) :801-+
[26]   Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus [J].
Dedrick, Rebekah M. ;
Guerrero-Bustamante, Carlos A. ;
Garlena, Rebecca A. ;
Russell, Daniel A. ;
Ford, Katrina ;
Harris, Kathryn ;
Gilmour, Kimberly C. ;
Soothill, James ;
Jacobs-Sera, Deborah ;
Schooley, Robert T. ;
Hatfull, Graham F. ;
Spencer, Helen .
NATURE MEDICINE, 2019, 25 (05) :730-+
[27]   The population genetics of pathogenicEscherichia coli [J].
Denamur, Erick ;
Clermont, Olivier ;
Bonacorsi, Stephane ;
Gordon, David .
NATURE REVIEWS MICROBIOLOGY, 2021, 19 (01) :37-54
[28]   Phage diversity, genomics and phylogeny [J].
Dion, Moira B. ;
Oechslin, Frank ;
Moineau, Sylvain .
NATURE REVIEWS MICROBIOLOGY, 2020, 18 (03) :125-138
[29]   The Role of Outer Membrane Proteins and Lipopolysaccharides for the Sensitivity of Escherichia coli Antimicrobial Peptides [J].
Ebbensgaard, Anna ;
Mordhorst, Hanne ;
Aarestrup, Frank M. ;
Hansen, Egon B. .
FRONTIERS IN MICROBIOLOGY, 2018, 9
[30]   Accelerated Profile HMM Searches [J].
Eddy, Sean R. .
PLOS COMPUTATIONAL BIOLOGY, 2011, 7 (10)