Three novel Enterobacter cloacae bacteriophages for therapeutic use from Ghanaian natural waters.
Enterobacter cloacae
/ virology
Ghana
Bacteriophages
/ genetics
Anti-Bacterial Agents
/ pharmacology
Phage Therapy
/ methods
Genome, Viral
Enterobacteriaceae Infections
/ therapy
Drug Resistance, Multiple, Bacterial
Finland
Humans
Microbial Sensitivity Tests
Ciprofloxacin
/ pharmacology
Meropenem
/ pharmacology
Journal
Archives of virology
ISSN: 1432-8798
Titre abrégé: Arch Virol
Pays: Austria
ID NLM: 7506870
Informations de publication
Date de publication:
05 Jul 2024
05 Jul 2024
Historique:
received:
24
11
2023
accepted:
15
05
2024
medline:
5
7
2024
pubmed:
5
7
2024
entrez:
5
7
2024
Statut:
epublish
Résumé
Infections caused by multidrug-resistant (MDR) bacteria are a growing global concern. Enterobacter cloacae complex (ECC) species are particularly adept at developing antibiotic resistance. Phage therapy is proposed as an alternative treatment for pathogens that no longer respond to antibiotics. Unfortunately, ECC phages are understudied when compared to phages of many other bacterial species. In this Ghanaian-Finnish study, we isolated two ECC strains from ready-to-eat food samples and three novel phages from natural waters against these strains. We sequenced the genomic DNA of the novel Enterobacter phages, fGh-Ecl01, fGh-Ecl02, and fGh-Ecl04, and assessed their therapeutic potential. All of the phages were found to be lytic, easy to propagate, and lacking any toxic, integrase, or antibiotic resistance genes and were thus considered suitable for therapy purposes. They all were found to be related to T4-type viruses: fGh-Ecl01 and fGh-Ecl04 to karamviruses and fGh-Ecl02 to agtreviruses. Testing of Finnish clinical ECC strains showed promising susceptibility to these novel phages. As many as 61.1% of the strains were susceptible to fGh-Ecl01 and fGh-Ecl04, and 7.4% were susceptible to fGh-Ecl02. Finally, we investigated the susceptibility of the newly isolated ECC strains to three antibiotics - meropenem, ciprofloxacin, and cefepime - in combination with the novel phages. The use of phages and antibiotics together had synergistic effects. When using an antibiotic-phage combination, even low concentrations of antibiotics fully inhibited the growth of bacteria.
Identifiants
pubmed: 38967872
doi: 10.1007/s00705-024-06081-9
pii: 10.1007/s00705-024-06081-9
doi:
Substances chimiques
Anti-Bacterial Agents
0
Ciprofloxacin
5E8K9I0O4U
Meropenem
FV9J3JU8B1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
156Informations de copyright
© 2024. The Author(s).
Références
Al-Kharousi ZS, Guizani N, Al-Sadi AM, Al-Bulushi IM, Shaharoona B (2016) Hiding in fresh fruits and vegetables: opportunistic pathogens may cross geographical barriers. Int J Microbiol 2016:4292417
pubmed: 26989419
pmcid: 4772400
doi: 10.1155/2016/4292417
Alcock BP, Raphenya AR, Lau TTY, Tsang KK, Bouchard M, Edalatmand A, Huynh W, Nguyen AV, Cheng AA, Liu S, Min SY, Miroshnichenko A, Tran HK, Werfalli RE, Nasir JA, Oloni M, Speicher DJ, Florescu A, Singh B, Faltyn M, Hernandez-Koutoucheva A, Sharma AN, Bordeleau E, Pawlowski AC, Zubyk HL, Dooley D, Griffiths E, Maguire F, Winsor GL, Beiko RG, Brinkman FSL, Hsiao WWL, Domselaar GV, McArthur AG (2020) CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res 48:D517–D525
pubmed: 31665441
Annavajhala MK, Gomez-Simmonds A, Uhlemann AC (2019) Multidrug-Resistant enterobacter cloacae complex emerging as a global, diversifying threat. Front Microbiol 10:44
pubmed: 30766518
pmcid: 6365427
doi: 10.3389/fmicb.2019.00044
Aziz RK, Bartels D, Best AA, DeJongh M, Disz T, Edwards RA, Formsma K, Gerdes S, Glass EM, Kubal M, Meyer F, Olsen GJ, Olson R, Osterman AL, Overbeek RA, McNeil LK, Paarmann D, Paczian T, Parrello B, Pusch GD, Reich C, Stevens R, Vassieva O, Vonstein V, Wilke A, Zagnitko O (2008) The RAST Server: rapid annotations using subsystems technology. BMC Genomics 9:75
pubmed: 18261238
pmcid: 2265698
doi: 10.1186/1471-2164-9-75
Brown ED, Wright GD (2016) Antibacterial drug discovery in the resistance era. Nature 529:336–343
pubmed: 26791724
doi: 10.1038/nature17042
Bryce J, Boschi-Pinto C, Shibuya K, Black RE, Refer WCHE (2005) WHO estimates of the causes of death in children. Lancet 365:1147–1152
pubmed: 15794969
doi: 10.1016/S0140-6736(05)71877-8
Cano EJ, Caflisch KM, Bollyky PL, Van Belleghem JD, Patel R, Fackler J, Brownstein MJ, Horne B, Biswas B, Henry M, Malagon F, Lewallen DG, Suh GA (2021) Phage therapy for limb-threatening prosthetic knee klebsiella pneumoniae infection: case report and in vitro characterization of anti-biofilm activity. Clin Infect Dis 73:e144–e151
pubmed: 32699879
doi: 10.1093/cid/ciaa705
Chan PP, Lowe TM (2019) tRNAscan-SE: Searching for tRNA Genes in Genomic Sequences. Methods Mol Biol 1962:1–14
pubmed: 31020551
pmcid: 6768409
doi: 10.1007/978-1-4939-9173-0_1
Christiana Cudjoe D, Balali GI, Titus OO, Osafo R, Taufiq M (2022) Food Safety in Sub-Sahara Africa, An insight into Ghana and Nigeria. Environ Health Insights 16:11786302221142484
pubmed: 36530486
pmcid: 9755555
doi: 10.1177/11786302221142484
Coil D, Jospin G, Darling AE (2015) A5-miseq: an updated pipeline to assemble microbial genomes from Illumina MiSeq data. Bioinformatics 31:587–589
pubmed: 25338718
doi: 10.1093/bioinformatics/btu661
de Jonge PA, Nobrega FL, Brouns SJJ, Dutilh BE (2019) Molecular and Evolutionary Determinants of Bacteriophage Host Range. Trends Microbiol 27:51–63
pubmed: 30181062
doi: 10.1016/j.tim.2018.08.006
De Oliveira DMP, Forde BM, Kidd TJ, Harris PNA, Schembri MA, Beatson SA, Paterson DL, Walker MJ (2020) Antimicrobial resistance in ESKAPE pathogens. Clin Microbiol Rev 33:e00181-19
El Haddad L, Harb CP, Gebara MA, Stibich MA, Chemaly RF (2019) A Systematic and critical review of bacteriophage therapy against multidrug-resistant ESKAPE organisms in humans. Clin Infect Dis 69:167–178
pubmed: 30395179
doi: 10.1093/cid/ciy947
Farris JS (1972) Estimating phylogenetic trees from distance matrices. Am Nat 106:645–668
doi: 10.1086/282802
Feglo P, Sakyi K (2012) Bacterial contamination of street vending food in Kumasi, Ghana. J Med Biomed Sci 1:1–8
Feng P, Weagant SD, Grant MA, Burkhardt W, Shellfish M, Water B (2013) Enumeration of Escherichia coli and the Coliform Bacteria. Bacteriological analytical manual. U.S. Food & Drug Administration, pp 1-13
Girlich D, Ouzani S, Emeraud C, Gauthier L, Bonnin RA, Le Sache N, Mokhtari M, Langlois I, Begasse C, Arangia N, Fournier S, Fortineau N, Naas T, Dortet L (2021) Uncovering the novel Enterobacter cloacae complex species responsible for septic shock deaths in newborns: a cohort study. Lancet Microbe 2:e536–e544
pubmed: 35544179
doi: 10.1016/S2666-5247(21)00098-7
Goodridge LD (2013) Bacteriophages for managing Shigella in various clinical and non-clinical settings. Bacteriophage 3:e25098
pubmed: 23819110
pmcid: 3694061
doi: 10.4161/bact.25098
Gordillo Altamirano FL, Barr JJ (2019) Phage therapy in the Postantibiotic Era. Clin Microbiol Rev 32:e00066-18
Igbinosa IH, Beshiru A, Egharevba NE, Igbinosa EO (2020) Distribution of enterobacteria in ready-to-eat food in cafeterias and retail food outlets in Benin City: public health implications. J Commun Med Prim Health Care 32:80–94
doi: 10.4314/jcmphc.v32i2.7
Imklin N, Sriprasong P, Thanantong N, Lekcharoensuk P, Nasanit R (2022) Characterization and complete genome analysis of a novel Escherichia phage, vB_EcoM-RPN242. Arch Virol 167:1675–1679
pubmed: 35598209
doi: 10.1007/s00705-022-05479-7
Iredell J, Brown J, Tagg K (2016) Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications. BMJ 352:h6420
pubmed: 26858245
doi: 10.1136/bmj.h6420
Joensen KG, Scheutz F, Lund O, Hasman H, Kaas RS, Nielsen EM, Aarestrup FM (2014) Real-time whole-genome sequencing for routine typing, surveillance, and outbreak detection of verotoxigenic Escherichia coli. J Clin Microbiol 52:1501–1510
pubmed: 24574290
pmcid: 3993690
doi: 10.1128/JCM.03617-13
Johnson M, Zaretskaya I, Raytselis Y, Merezhuk Y, McGinnis S, Madden TL (2008) NCBI BLAST: a better web interface. Nucleic Acids Res 36:W5-9
pubmed: 18440982
pmcid: 2447716
doi: 10.1093/nar/gkn201
Koonin EV, Dolja VV, Krupovic M, Varsani A, Wolf YI, Yutin N, Zerbini FM, Kuhn JH (2020) Global organization and proposed megataxonomy of the virus world. Microbiol Mol Biol Rev 84:e00061-19
Kropinski AM, Mazzocco A, Waddell TE, Lingohr E, Johnson RP (2009) Enumeration of bacteriophages by double agar overlay plaque assay. Methods Mol Biol 501:69–76
pubmed: 19066811
doi: 10.1007/978-1-60327-164-6_7
Kutateladze M, Adamia R (2010) Bacteriophages as potential new therapeutics to replace or supplement antibiotics. Trends Biotechnol 28:591–595
pubmed: 20810181
doi: 10.1016/j.tibtech.2010.08.001
Leskinen K, Tuomala H, Wicklund A, Horsma-Heikkinen J, Kuusela P, Skurnik M, Kiljunen S (2017) Characterization of vB_SauM-fRuSau02, a twort-like bacteriophage isolated from a therapeutic phage cocktail. Viruses 9:258
Letunic I, Bork P (2021) Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 49:W293–W296
pubmed: 33885785
pmcid: 8265157
doi: 10.1093/nar/gkab301
Luong T, Salabarria AC, Roach DR (2020) Phage Therapy in the Resistance Era: Where Do We Stand and Where Are We Going? Clin Ther 42:1659–1680
pubmed: 32883528
doi: 10.1016/j.clinthera.2020.07.014
Manohar P, Tamhankar AJ, Lundborg CS, Nachimuthu R (2019) Therapeutic Characterization and Efficacy of Bacteriophage Cocktails Infecting Escherichia coli, Klebsiella pneumoniae, and Enterobacter Species. Front Microbiol 10:574
pubmed: 30949158
pmcid: 6437105
doi: 10.3389/fmicb.2019.00574
McArthur AG, Waglechner N, Nizam F, Yan A, Azad MA, Baylay AJ, Bhullar K, Canova MJ, De Pascale G, Ejim L, Kalan L, King AM, Koteva K, Morar M, Mulvey MR, O’Brien JS, Pawlowski AC, Piddock LJ, Spanogiannopoulos P, Sutherland AD, Tang I, Taylor PL, Thaker M, Wang W, Yan M, Yu T, Wright GD (2013) The comprehensive antibiotic resistance database. Antimicrob Agents Chemother 57:3348–3357
pubmed: 23650175
pmcid: 3697360
doi: 10.1128/AAC.00419-13
Meier-Kolthoff JP, Auch AF, Klenk HP, Goker M (2013) Genome sequence-based species delimitation with confidence intervals and improved distance functions. BMC Bioinformatics 14:60
pubmed: 23432962
pmcid: 3665452
doi: 10.1186/1471-2105-14-60
Meier-Kolthoff JP, Goker M (2017) VICTOR: genome-based phylogeny and classification of prokaryotic viruses. Bioinformatics 33:3396–3404
pubmed: 29036289
pmcid: 5860169
doi: 10.1093/bioinformatics/btx440
Meier-Kolthoff JP, Carbasse JS, Peinado-Olarte RL, Goker M (2022) TYGS and LPSN: a database tandem for fast and reliable genome-based classification and nomenclature of prokaryotes. Nucleic Acids Res 50:D801–D807
pubmed: 34634793
doi: 10.1093/nar/gkab902
Mezzatesta ML, Gona F, Stefani S (2012) Enterobacter cloacae complex: clinical impact and emerging antibiotic resistance. Future Microbiol 7:887–902
pubmed: 22827309
doi: 10.2217/fmb.12.61
Miltgen G, Garrigos T, Cholley P, Deleume M, Allou N, Allyn J, Wilkinson DA, Lugagne N, Belmonte O, Bertrand X, Hocquet D, Mavingui P (2021) Nosocomial cluster of carbapenemase-producing Enterobacter cloacae in an intensive care unit dedicated COVID-19. Antimicrob Resist Infect Control 10:151
pubmed: 34674756
pmcid: 8529563
doi: 10.1186/s13756-021-01022-6
Moraru C, Varsani A, Kropinski AM (2020) VIRIDIC-A novel tool to calculate the intergenomic similarities of prokaryote-infecting viruses. Viruses 12:1268
Moraru C (2023) VirClust-A tool for hierarchical clustering, core protein detection and annotation of (Prokaryotic) viruses. Viruses 15:1007
Morens DM, Folkers GK, Fauci AS (2004) The challenge of emerging and re-emerging infectious diseases. Nature 430:242–249
pubmed: 15241422
pmcid: 7094993
doi: 10.1038/nature02759
Nyenje ME, Odjadjare CE, Tanih NF, Green E, Ndip RN (2012) Foodborne pathogens recovered from ready-to-eat foods from roadside cafeterias and retail outlets in Alice, Eastern Cape Province, South Africa: public health implications. Int J Env Res Pub He 9:2608–2619
doi: 10.3390/ijerph9082608
Patpatia S, Schaedig E, Dirks A, Paasonen L, Skurnik M, Kiljunen S (2022) Rapid hydrogel-based phage susceptibility test for pathogenic bacteria. Front Cell Infect Mi 12:1032052
Pendleton JN, Gorman SP, Gilmore BF (2013) Clinical relevance of the ESKAPE pathogens. Expert Rev Anti Infect Ther 11:297–308
pubmed: 23458769
doi: 10.1586/eri.13.12
Pereira S, Pereira C, Santos L, Klumpp J, Almeida A (2016) Potential of phage cocktails in the inactivation of Enterobacter cloacae–An in vitro study in a buffer solution and in urine samples. Virus Res 211:199–208
pubmed: 26541317
doi: 10.1016/j.virusres.2015.10.025
Cook R, Brown N, Redgwell T, Rihtman B, Barnes M, Clokie M, Stekel DJ, Hobman J, Jones MA, Millard A (2021) Infrastructure for a PHAge reference database: identification of large-scale biases in the current collection of cultured phage genomes. PHAGE
Ren H, Li Z, Li X, Wang L, Xu Y (2020) Genome sequence analysis of a novel Enterobacter cloacae phage, Ec_L1, belonging to the genus Eclunavirus. Arch Virol 165:1929–1932
pubmed: 32514690
doi: 10.1007/s00705-020-04672-w
Salem M, Pajunen MI, Jun JW, Skurnik M (2021) T4-like bacteriophages isolated from pig stools infect yersinia pseudotuberculosis and yersinia pestis using LPS and OmpF as receptors. Viruses 13:296
Sambrook J, Russell DW (2001) Molecular Cloning, a Laboratory Manual, 3rd edn. Cold Spring Harbor Laboratory Press, New York, NY, USA
Sarker SA, McCallin S, Barretto C, Berger B, Pittet AC, Sultana S, Krause L, Huq S, Bibiloni R, Bruttin A, Reuteler G, Brussow H (2012) Oral T4-like phage cocktail application to healthy adult volunteers from Bangladesh. Virology 434:222–232
pubmed: 23102968
doi: 10.1016/j.virol.2012.09.002
Sarker SA, Brussow H (2016) From bench to bed and back again: phage therapy of childhood Escherichia coli diarrhea. Ann N Y Acad Sci 1372:42–52
pubmed: 27197768
doi: 10.1111/nyas.13087
Sarker SA, Sultana S, Reuteler G, Moine D, Descombes P, Charton F, Bourdin G, McCallin S, Ngom-Bru C, Neville T, Akter M, Huq S, Qadri F, Talukdar K, Kassam M, Delley M, Loiseau C, Deng Y, El Aidy S, Berger B, Brussow H (2016) Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh. EBioMedicine 4:124–137
pubmed: 26981577
pmcid: 4776075
doi: 10.1016/j.ebiom.2015.12.023
Seeberg AH, Tolxdorff-Neutzling RM, Wiedemann B (1983) Chromosomal beta-lactamases of Enterobacter cloacae are responsible for resistance to third-generation cephalosporins. Antimicrob Agents Chemother 23:918–925
pubmed: 6351733
pmcid: 185004
doi: 10.1128/AAC.23.6.918
Seed KD (2015) Battling Phages: How Bacteria Defend against Viral Attack. PLoS Pathog 11:e1004847
pubmed: 26066799
pmcid: 4465916
doi: 10.1371/journal.ppat.1004847
Skurnik M, Strauch E (2006) Phage therapy: facts and fiction. Int J Med Microbiol 296:5–14
pubmed: 16423684
doi: 10.1016/j.ijmm.2005.09.002
Skurnik M, Jaakkola S, Mattinen L, von Ossowski L, Nawaz A, Pajunen MI, Happonen LJ (2021) Bacteriophages fEV-1 and fD1 infect yersinia pestis. Viruses 13:1384
Skurnik M (2022) Can bacteriophages replace antibiotics? Antibiotics (Basel) 11:575
Smith HZ, Kendall B (2021) Carbapenem Resistant Enterobacteriaceae. StatPearls, Treasure Island (FL)
Suh GA, Lodise TP, Tamma PD, Knisely JM, Alexander J, Aslam S, Barton KD, Bizzell E, Totten KMC, Campbell JL, Chan BK, Cunningham SA, Goodman KE, Greenwood-Quaintance KE, Harris AD, Hesse S, Maresso A, Nussenblatt V, Pride D, Rybak MJ, Sund Z, van Duin D, Van Tyne D, Patel R, Antibacterial Resistance Leadership G (2022) Considerations for the Use of Phage Therapy in Clinical Practice. Antimicrob Agents Chemother 66:e0207121
pubmed: 35041506
doi: 10.1128/aac.02071-21
Sulakvelidze A, Alavidze Z, Morris JG Jr (2001) Bacteriophage therapy. Antimicrob Agents Chemother 45:649–659
pubmed: 11181338
pmcid: 90351
doi: 10.1128/AAC.45.3.649-659.2001
Thanh NC, Nagayoshi Y, Fujino Y, Iiyama K, Furuya N, Hiromasa Y, Iwamoto T, Doi K (2020) Characterization and Genome Structure of Virulent Phage EspM4VN to Control Enterobacter sp. M4 Isolated From Plant Soft Rot. Front Microbiol 11:885
pubmed: 32582040
pmcid: 7283392
doi: 10.3389/fmicb.2020.00885
Wang G, Clark CG, Rodgers FG (2002) Detection in Escherichia coli of the genes encoding the major virulence factors, the genes defining the O157:H7 serotype, and components of the type 2 Shiga toxin family by multiplex PCR. J Clin Microbiol 40:3613–3619
pubmed: 12354854
pmcid: 130888
doi: 10.1128/JCM.40.10.3613-3619.2002
Wang K, Tamayo MG, Penner TV, Cook BWM, Court DA, Theriault SS (2020) Characterization of the enterobacter phage vB_EclM_CIP9. Microbiol Resour Announc 9:e01600-19
Yakubu B, Boniface ND, Umaru DA (2011) Public health risk of O157 and Non-O157 Shiga toxin producing Escherichia coli strains in a semi-urban environment in Nigeria. Afr J Microbiol Res 5:5636–5643