Pathogenic potential of ornithogenic Escherichia coli strains detected in the Earth's polar regions

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Introduction

Escherichia coli is a unique microorganism capable of causing infections in a wide range of clinical manifestations in humans and various animals, which determines the importance of monitoring the spread of its main pathotypes in nature, agriculture and human society [1].

One of such pathotypes monitored under the One Health concept is avian pathogenic E. coli (avian pathogenic E. coli — APEC), which belongs to the group of pathogens of extraintestinal localization (extraintestinal pathogenic E. coli — ExPEC) [2, 3].

Although the possibility of direct zoonotic transmission of APEC from birds to humans is debatable [4], numerous studies show that APEC are genetically similar to human ExPEC (uropathogenic E. coli (UPEC) and E. coli associated with neonatal meningitis (NMEC)). There are studies supporting the commonality of pathogenicity factors in human APEC and ExPEC isolates. For example, the virulence genes iroN, traT, iucD, cvi/cva, ibeA, gimB, tia, neuC, kpsMTII, tsh, iss, sitD, chuA, fyuA, irp2, vat, malX and pic are present in the genomes of both APEC, UPEC and NMEC [5].

The similarity between the virulomes of APEC strains and human ExPEC emphasizes the potential threat of avian-associated zoonotic infections. Importantly, wild birds may act as a facilitator of the spread of APEC-associated virulence and antimicrobial resistance genes. For example, it has been shown that antibiotic resistance determinants can be transmitted from wild geese and swan strains of Enterobacteriaceae to strains in domestic birds, and from the latter to humans [6, 7].

The circumpolar regions of the Earth represent a unique geographical environment in which, despite extreme climatic conditions, the high productivity of shelf seas [8] maintains a high level of faunal biodiversity. The coasts of the Arctic and Southern Oceans within the continental Antarctic, Antarctic and sub-Antarctic archipelagos are points of attraction for billions of migrating birds, a significant part of which make long, including transcontinental flights. For example, the Palaearctic-African migration system alone includes 2.1 billion migrating individuals [9]. Colonies of migrating birds in high latitudes can be points of active intraspecies and interspecies contacts between birds and other animals, accompanied by the exchange of microbiota, including the pathogenic part of it [10].

In this regard, it seems important to study the distribution of bird-associated pathogens in ornithogenic ecosystems formed around bird colonies on the coasts of the Arctic and Antarctic seas.

At the same time, phylogeography and genetic features of such an actual object of epidemiologic and epizootologic surveillance as E. coli remains virtually unstudied in polar regions.

The aim of the study is the assessment of the pathogenic potential of E. coli strains distributed in the polar regions of the Earth based on the analysis of the genomes of these bacteria from a sample characterizing typical ornithogenic ecosystems of the Arctic and Antarctica.

Materials and methods

Collections of E. coli strains isolated from ornithogenic biological material (droppings, feces and carcasses of fallen birds, nest substrates, microbial mats of water bodies contaminated with bird droppings) during several expeditions were used in this study.

In particular, during the implementation of the scientific program of the Russian Arctic expedition on the Svalbard archipelago in 2018, 28 samples of ornithogenic material were collected, from which 6 isolates were isolated, in the expedition of Arctic Floating University (2023) — 8 isolates from 38 samples, in the 68th Russian Antarctic expedition of 2022–2023 — 19 isolates from 29 samples.

The present study describes the E. coli cultures isolated in the bird colonies of the Svalbard archipelago (West Spitsbergen Island), Novaya Zemlya and Franz Josef Land archipelagos, as well as on the islands of the Haswell Archipelago, which became one of the key ornithological territories of East Antarctica due to many thousands colonies of Adelie and Emperor penguins.

Furthermore, five E. coli strains isolated from cloacal flushes during bird ringing in the spring-summer period of 2023 at the Ladoga ornithological station (Nizhne-Svirsky Reserve, Gumbaritsy tract, Leningrad region) were used as comparison strains. All Arctic and Antarctic cultures were isolated without the use of enrichment methods using dense nutrient media when cultured directly in the field, as described previously [11].

The procedure of biological material sampling was carried out in accordance with generally accepted ethical normsю The research protocol was approved by the Ethics Committee of the which is confirmed by the decision of the Local Ethics Committee of North-Western State Medical University named after I.I. Mechnikov (Protocol No. 3, March 13, 2024).

Species identification of the isolated strains was performed using time-of-flight mass spectrometry (MALDI-TOF) on a Bactoscreen instrument (Litech). Mass spectra were analyzed using Biotyper 3.1 software.

As a result of random sampling, 16 strains were selected for whole-genome sequencing (WGS), followed by annotation and evaluation of pathogenic potential.

Information on the sources of cultures whose genomes were sequenced is presented in Table 1.

 

Table 1. Characteristics of studied isolates

No.	Isolates	Place of isolation, coordinates	Source of isolation
Isolates associated with bird ecosystems of the Arctic
1	67Spits	Svalbard archipelago, Barentsburg, 78°03'N 14°16'E	Feces of Rissa trydacyla
2	70_2Spits	Svalbard archipelago, Gronfjorden Bay coast, N 78°00'36.2"N 14°18'09.7"E	Feces of Rissa trydacyla
3	89Spits	Svalbard archipelago, Barentsburg, 78°03'N 14°16'E	Feces of Anser brachyrhynchus
4	97Spits	Svalbard archipelago, Barentsburg, 78°03'N 14°16'E	Feces of Anser brachyrhynchus
5	AFU_2	Yugorsky Peninsula, White Nose Cape, 69°36'14.7"N 60°12'08.1"E	Feces of Somateria mollissima
6	AFU_32_1	Novaya Zemlya archipelago, Cape of Desire, 76°57'18.5"N 68°34'41.9"E	Feces of polar bear near the Rissa trydacyla bird spot
7	AFU_33_1	Novaya Zemlya archipelago, North Island, Cape of Desire, 76°57'18.5"N 68°34'41.9"E	Nests in the bird spot of Rissa trydacyla
8	AFU_43_1	Архипелаг Земля Франца-Иосифа, о-в Вильчека, 79°53'41.8"N 58°44'07.2"E Franz Josef Archipelago, Wilczek Island, 79°53'41.8"N 58°44'07.2"E	Egg shell of Uria lomvia
9	AFU_55_1	Franz Josef Archipelago, Komsomolskie islands (South Island), 80°34'48.3"N 58°32'40.2"E	Рond near the Sterna paradisaea bird spot
Isolates associated with bird ecosystems of the Antarctic
10	15myr	West Antarctica, Queen Mary Land, Haswell Archipelago, Haswell Island, 66°31'36.6"S 93°00'20.8"E	Adelie penguin (Pygoscelis adeliae), cloaca sample
11	17_1myr	West Antarctica, Queen Mary Land, Haswell Archipelago, Haswell Island, 66°31'36.6"S 93°00'20.8"E	Stomach sample from Fulmarus glacialoides
12	28myr	West Antarctica, Queen Mary Land, Haswell Archipelago, Tokareva Island, 66°32'06.1"S 92°58'25.8"E	Feces of Adelie penguin (Pygoscelis adeliae)
Isolates form birds in European region of Russia, Ladoga Ornithological Station (LOS)
13	LOS_49	Nizhne-Svirskiy Reserve, LOS, 60°40'35.0"N 32°56'27.2"E	Сloaca sample from Poecile palustris
14	LOS_51	Nizhne-Svirskiy Reserve, LOS, 60°40'35.0"N 32°56'27.2"E	Anas crecca feces
15	LOS_52	Nizhne-Svirskiy Reserve, LOS, 60°40'35.0"N 32°56'27.2"E	Сloaca sample from Turdus pilaris
16	LOS_54	Nizhne-Svirskiy Reserve, LOS, 60°40'35.0"N 32°56'27.2"E	Сloaca sample from Turdus pilaris

 

Biolabmix kits were used for genomic DNA isolation. Genomic sequencing was performed using BGI technology at the Pasteur Research Institute of Epidemiology and Microbiology. Genome annotation was performed using the RAST server (https://rast.nmpdr.org/rast.cgi), drug resistance and virulence genes were searched using the ABRicate v 0.8 program (https://github.com/tseemann/abricate), and the MEGARes (https://megares.meglab.org/amrplusplus/latest/html), Comprehensive Antibiotic Resistance Database, CARD 3.0.2 (https://card.mcmaster.ca/analyze/rgi) and VFDB (https://www.mgc.ac.cn/VFs/) databases were used for this purpose.

The antigenic structure of E. coli was determined using the online tool SerotypeFinder 2.0 (https://cge.food.dtu.dk/services/SerotypeFinder/). The MLST 2.0 resource (https://cge.food.dtu.dk/services/MLST/) was used to evaluate the results of multilocus sequencing-typing (MLST). The WGS typing results for bovine genes obtained using the online tool cgMLSTFinder 1.2 (https://cge.food.dtu.dk/services/cgMLSTFinder/) were compared with the data on the corresponding cgMLST types deposited in the EnteroBase database (https://enterobase.warwick.ac.uk/species/index/ecoli), allowing for differences (Max Number MisMatches) of no more than 20 single polymorphisms (SNPs).

Results

The annotation of genomes allowed us to determine their belonging to different STs in MLST and WGS-typing schemes. The main characteristics of the studied genomes and access numbers to their sequences are presented in Table 2.

 

Table 2. Genetic characteristics of isolated E. coli strains

Strain	Region of isolation	Serotype	Sequence type (ST)	ST by core genome (cgST)	GenBank access number
67Spits	Arctic	O4:H5	12	10054	JAYEAG010000000
70_2Spits	Arctic	O43:H2	937	28072	JAYEAE000000000.1
89Spits	Arctic	O83:H1	135	87221	JAYEAD000000000.1
97Spits	Arctic	O166:H49	1246	162	JAYEAC000000000.1
AFU_2	Arctic	O93:H16	8097	132840	JAYEAJ000000000
AFU_32_1	Arctic	O54:H45	491	11903	JAYEAI000000000
AFU_33_1	Arctic	O15:H2	69	189219	JAYEAH000000000
AFU_43_1	Arctic	O9:H49	6163*	1429	JBIQXY000000000
AFU_55_1	Arctic	O39:H4	1155	196482	JBIQXZ000000000
15myr	Antarctic	O8:H7	127	196780	JBIQXV000000000
17_1myr	Antarctic	O6:H31	196	133718	JBIQXW000000000
28myr	Antarctic	O182:H38	1632	94237	JBIQXX000000000
LOS_49	European Russia	O8:H5	2594*	47119	JBIQYA000000000
LOS_51	European Russia	O85:H8	297	114487	JBIQYB000000000
LOS_52	European Russia	N/i	1333*	119313	JBIQYC000000000
LOS_54	European Russia	N/i	58	126100	JBIQYD000000000

Note. *Genotypes with single nucleotide polymorphisms in genes for which sequencing-typing was performed, distinguishing them from the specified sequence types. N/I — not identified.

 

Genes encoding AmpC-like beta-lactamases, the hyperproduction of which provides resistance to cephalosporins, were identified in all genomes studied [12]. In addition, the genome of the Arctic strain E. coli 33-1 was characterized by the presence of a plasmid of about 78,000 bp containing the gene for the extended-spectrum beta-lactamase TEM-1b and transposon Tn1721, which includes tetracycline resistance genes (tetA-tetR). Numerous pathogenicity factor genes associated with adhesion, invasion and iron capture were detected in the genomes of the studied microorganisms (Table 3).

 

Table 3. Pathogenic determinants in studied E. coli strains

Рathogenic determinants

17myr

15myr

28myr

67Spits

70_2Spits

89Spits

97Spits

AFU_2

AFU_32_1

AFU_33_1

AFU_43_1

AFU_55_1

LOS_49

LOS_51

LOS_52

LOS_54

Hemolysins

Hemolysin A (hlyA)

+

–

–

+

–

–

–

–

–

–

–

–

–

–

–

–

Bird hemolysin E (hlyE)

–

+

+

–

+

–

+

+

–

+

+

–

–

+

–

+

Hemolysin F (hlyF)

+

+

–

–

–

–

–

–

–

+

–

+

+

–

–

+

Siderophores

Enterobactin operon

+

–

–

–

–

–

–

–

–

–

–

+

+

–

–

+

Yersiniabactin operon

+

–

–

+

–

+

–

–

+

+

–

+

–

+

+

–

Aerobactin operon

+

+

–

–

–

–

–

–

–

+

–

+

–

–

–

–

Toxins

Heat-stable enterotoxin EAST-1

–

–

–

–

–

–

+

–

+

–

–

–

–

–

+

+

Subtilase

–

–

–

–

–

–

–

–

+

–

–

–

–

–

–

–

Сytolethal distending toxin (cdt)

–

–

–

–

–

–

–

–

–

–

–

–

–

–

+

–

Adhesion, invasion and biofilm formation determinants

Аdhesin AIDA-I

–

–

–

+

–

–

–

–

–

–

–

–

+

–

–

+

Аggregation substance Tia

–

–

–

–

–

–

–

–

–

–

–

–

–

–

–

+

Gen eilA homologue (Salmonella HilA homolog)

–

–

–

–

–

–

–

–

–

+

+

–

–

–

–

–

Enteroaggregative protein (air)

–

–

–

–

–

–

–

–

–

+

+

–

–

–

–

–

Factor of invasion of brain endothelium (ibeA)

–

–

–

–

–

+

–

–

–

–

–

+

+

–

+

–

Serum survival gene (iss)

+

–

+

–

+

–

+

–

–

+

–

+

+

–

–

+

Аrylsulfatase AslA

+

–

+

+

–

+

–

–

–

–

–

–

+

–

+

–

Heat-resistant agglutinin (hra)

+

–

–

+

+

–

+

–

–

–

–

–

–

–

–

+

Сytotoxic necrotizing factor (cnf)

+

–

–

+

–

–

–

–

–

–

–

–

–

–

–

–

Uropathogenic specific protein (usp)

+

–

–

+

–

+

–

–

–

–

–

+

–

–

–

–

Сurlin CsgA

+

+

+

+

+

+

+

+

+

–

+

+

+

+

+

Homologue of the Shigella flexneri SHI-2 pathogenicity island gene shiA

+

–

+

+

–

–

–

–

–

–

–

–

–

–

–

+

Intimin-like adhesin FdeC

+

+

–

+

+

+

+

+

+

–

+

–

–

–

+

+

Serine protease autotransporters of Enterobacteriaceae (SPATE)

+

–

–

+

–

+

–

–

+

+

–

+

+

–

+

–

 

The wide representation of ExPEC pathogenicity factor genes in the genomes of the strains under study raises the question of the potential association of these strains with cases of infectious diseases in humans.

Using the EnteroBase database (https://enterobase.warwick.ac.uk/species/index/ecoli), which accumulates global data on cgMLST genotyping results and currently includes information on more than 340,000 E. coli strains, a search was carried out for information on the geographical distribution of cgSTs identified in this study and their sources of isolation. The information was retrieved from the metadata provided in EnteroBase database for 11 STs (Table 4).

 

Table 4. Geographical distribution and isolation sources of sequence types (cgST) of the identified strains

Sequence type by core genome (cgST)	Region (regions) of isolation	Source of isolation	Reference number of the Sequence Read Archive (SRA) for strains most similar to the identified STs
10054	Europe, Anand Islands	Human (blood culture)	ERR434967
28072	USA	Livestock (cows)	SRR3972294
162	Australia	Chroicocephalus novaehollandiae	SRR24017969
132840	USA	Livestock (calves)	SRR26082289
11903	USA	Human (patient with urinary tract infection)	SRR1314409
189219	USA, Spain, Brazil, Denmark, UK	Chicken, human (blood culture and urine during urinary tract infection)	SRR17774295, ERR13306341, ERR4014451, SRR21849316 SRR21846782
196780	USA	Livestock (cows)	SRR19171807
133718	UK	Wild birds (Anseriformes)	SRR11410512
114487	USA	Beef	SRR10156198
119313	Netherlands	Human (blood culture)	ERR3650458
126100	Sweden	Poultry	SRR14477383

 

Discussion

In this study, an attempt was made to generate a sample of E. coli strains associated with high-latitude ornithogenic ecosystems typical of circumpolar regions in both the Northern and Southern Hemispheres.

In the Arctic, our studies focused on strains associated with marine colonial birds (Long-tailed Duck, Thick-billed Buzzards) and goose species (Bean Goose, Eiders). These bird species differ both in the ecological niches they occupy and in the duration and directions of migration, which may influence the structure of their microbiota, determining the probability of colonization by different E. coli genotypes.

At the same time, it is necessary to take into account the possibility of forming a single reservoir for populations of this microorganism along the entire coast of the Arctic Ocean, determined by bird migrations in the meridional direction. Thus, it was recently found out that a significant part of the kittiwake population migrates from the South Island of Novaya Zemlya to the wintering grounds on the coast of the North Pacific Ocean [13]. The spread of pathogens with Arctic migratory birds (predominantly from the goose group) simultaneously in latitudinal and meridional directions was previously shown for influenza viruses [14]. It should be noted that bean geese, the strains from which were studied in this research, make seasonal migrations from the Svalbard archipelago to wintering grounds in Belgium and the Netherlands, and against the background of global climate change in the Arctic, these birds are actively exploring Novaya Zemlya as well [15].

Three Antarctic strains, whose genomes were characterized in the present study, were isolated in the territory of Adelie penguin colonies on the islands of the Haswell Archipelago in East Antarctica. In spite of the fact that penguins of this species are endemic to Antarctica, in the territories of the colonies they neighbor also with long-distance migratory species of birds. For example, a frequent inhabitant of the Haswell Archipelago, the south polar skua, is able to make long seasonal migrations and reach the North Pacific and the North Atlantic [16]. Thus, the populations of Antarctic birds are not isolated from the global circulation of pathogens, as evidenced, in particular, by the circulation in the Antarctic of influenza virus strains identical to those isolated in other geographical regions [17].

Analysis of the geographical distribution of ST E. coli determined by the cgMLST method demonstrated their cosmopolitanism, which was manifested by the detection of identical cgST in geographically distant regions of the planet. For example, cgST 133718 was detected in Antarctica (strain 17_1myr) and Great Britain, and cgST 11903, to which strain 32-1 from the northernmost point of the New Earth belonged, was previously detected in the USA.

Despite the fact that all the strains studied belong to different genetic lineages (ST and serotypes), they are all united by the presence of an extensive virulome. As shown in Table 3, all strains from polar regions have a set of virulence factors that allow them to be considered as potential agents of human infections. In this respect, in general, they do not differ from the strains isolated from birds in the Leningrad Region.

Thus, 10 out of 12 polar strains contained genes or combinations of genes determining the synthesis of hemolysins A, E and F, which together with siderophores of the enterobactin, aerobactin and yersinibactin clusters participate in iron capture during the infection process [18]. It should be noted that the genes of the yersinibactin operon, found in half of the Arctic and Antarctic cultures, are part of the high pathogenicity island. This mobile genetic element is associated, as previously shown, with virulent UPECs [19].

The identified virulence factors for which localization in mobile genetic elements has been described include the uropathogenicity protein. The importance of this factor in damaging mammalian cells has been demonstrated, which is essential in the development of urinary tract infections [20].

In the studied sample, strains marking the enteroaggregative E. coli (EAEC) pathotype were also identified, in particular, the eilA virulence regulator gene (Salmonella HilA homolog) and the enteroaggregative protein gene (air), common in EAEC, were detected in the genomes of strains AFU-33-1 and AFU-43-1 from Novaya Zemlya and Franz Josef Land. The strain AFU-33-1 belongs to ST 189219 according to cgMLST results, which is widely represented in a number of European countries, USA and Brazil as a pathogen of generalized human infections. Thus, the spread of a peculiar epidemic clone of E. coli was observed in territories where there were no permanent human settlements.

In general, the spread of global genetic lineages of E. coli in high latitudes is consistent with the notion that the Rapoport Rule is observed for human pathogens, which states that as one moves from the equator to the poles, the distribution ranges of species or other taxonomic groupings increases [21].

The search for antimicrobial resistance genes in the genomes of E. coli strains carried out in this study indicates the absence (within our sample) of critical determinants of drug resistance. Nevertheless, the presence of genetic determinants of resistance to cephalosporins and tetracycline in the genome of the Arctic strain AFU 33-1 indicates the possibility of circulation of mobile genetic elements carrying these genes in the wild and their preservation in the microbiome of Arctic animals in the absence of antibiotic pressure.

Conclusion

The results of the study indicate the circulation of E. coli strains with strong pathogenic potential in high-latitude Arctic and Antarctic ornithogenic ecosystems. The analysis of the genomic data indicates the presence of genetic lineages that are geographically widespread in these regions, highlighting the importance of monitoring for epidemic clones of E. coli, together with monitoring for other pathogens, in high-latitude bird colonies.

About the authors

Batyrbek I. Aslanov

North-Western State Medical University named after I.I. Mechnikov

Email: phage1@yandex.ru
ORCID iD: 0000-0002-6890-8096

D. Sci. (Med.), Head, Department of epidemiology, parasitology and disinfection, Head, Laboratory of molecular epidemiology and bacteriophage research

Россия, Saint Petersburg

Daniil V. Azarov

North-Western State Medical University named after I.I. Mechnikov; Institute of Experimental Medicine

Email: phage1@yandex.ru
ORCID iD: 0000-0003-2483-5144

Cand. Sci. (Med.), Head, Laboratory of innovative methods of microbiological monitoring, Scientific and Educational Center of the National Center of Medical Sciences, Center for Personalized Medicine, senior researcher, Laboratory of molecular epidemiology and bacteriophage research

Россия, Saint Petersburg; Saint Petersburg

Maria A. Makarova

North-Western State Medical University named after I.I. Mechnikov; Saint Petersburg Pasteur Institute, Saint Petersburg

Email: phage1@yandex.ru
ORCID iD: 0000-0003-3600-2377

D. Sci. (Med.), leading researcher, Head, Laboratory of intestinal infections, Associate Professor, Department of medical microbiology

Россия, Saint Petersburg; Saint Petersburg

Elizaveta G. Marysheva

Saint Petersburg State University

Email: phage1@yandex.ru
ORCID iD: 0009-0000-8241-5290

student, Faculty of biology and soil science

Россия, Saint Petersburg

Lyudmila A. Kraeva

Saint Petersburg Pasteur Institute

Email: phage1@yandex.ru
ORCID iD: 0000-0002-9115-3250

D. Sci. (Med.), Professor, Head, Laboratory of medical bacteriology

Россия, Saint Petersburg

Aleksey S. Mokhov

North-Western State Medical University named after I.I. Mechnikov

Email: phage1@yandex.ru
ORCID iD: 0000-0002-1519-5299

Cand. Sci. (Med.), Assistant, Department of epidemiology, parasitology and disinfection

Россия, Saint Petersburg

Ekaterina A. Lebedeva

North-Western State Medical University named after I.I. Mechnikov

Email: phage1@yandex.ru
ORCID iD: 0000-0001-9547-0192

Cand. Sci. (Med.), Assistant Professor, Department of epidemiology, parasitology and disinfection, senior researcher, Laboratory of molecular epidemiology and bacteriophage research

Россия, Saint Petersburg

Nikita E. Goncharov

Saint Petersburg Pasteur Institute

Email: phage1@yandex.ru
ORCID iD: 0000-0002-6097-5091

junior researcher, Laboratory of medical bacteriology

Россия, Saint Petersburg

Natalya V. Lebedeva

Murmansk Marine Biological Institute

Email: phage1@yandex.ru
ORCID iD: 0000-0003-3545-753X

D. Sci. (Biol.), Professor, chief researcher, Laboratory of ornithology and parasitology

Россия, Murmansk

Dmitry A. Starikov

Nizhne-Svirsky State Nature Reserve

Email: phage1@yandex.ru
ORCID iD: 0000-0002-3721-8615

Cand. Sci. (Biol.), deputy director for science

Россия, Lodeynoye Pole

Victoria V. Kolodzhieva

North-Western State Medical University named after I.I. Mechnikov

Email: phage1@yandex.ru
ORCID iD: 0000-0002-1537-211X

Cand. Sci. (Med.), Associate Professor, Department of epidemiology, parasitology and disinfection, senior researcher, Laboratory of molecular epidemiology and bacteriophage research

Россия, Saint Petersburg

Dmitry E. Polev

Saint Petersburg Pasteur Institute

Email: phage1@yandex.ru
ORCID iD: 0000-0001-9679-2791

Cand. Sci. (Biol.), senior researcher, Metagenomic research group, Epidemiology department

Россия, Saint Petersburg

Artemy E. Goncharov

North-Western State Medical University named after I.I. Mechnikov; Institute of Experimental Medicine

Author for correspondence.
Email: phage1@yandex.ru
ORCID iD: 0000-0002-5206-6656

D. Sci. (Med.), Head, Laboratory of functional genomics and proteomics of microorganisms, Professor, Department of Epidemiology, parasitology and disinfection, leading researcher, Laboratory of molecular epidemiology and bacteriophage research

Россия, Saint Petersburg; Saint Petersburg

References

Supplementary files