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S.V. Shilov

JSC “Scientific Center of Anti-Infectious Drugs”, al-Farabi ave., 75a, Almaty, 050060, Kazakhstan

I.S. Korotetskiy

JSC “Scientific Center of Anti-Infectious Drugs”, al-Farabi ave., 75a, Almaty, 050060, Kazakhstan

O.N. Reva

Centre for Bioinformatics and Computational Biology, Department of Biochemistry, Genetics, and Microbiology, University of Pretoria, Pretoria, South Africa

T.V. Kuznetsova

JSC “Scientific Center of Anti-Infectious Drugs”, al-Farabi ave., 75a, Almaty, 050060, Kazakhstan

N.V. Zubenko

JSC “Scientific Center of Anti-Infectious Drugs”, al-Farabi ave., 75a, Almaty, 050060, Kazakhstan

L.N. Ivanova

JSC “Scientific Center of Anti-Infectious Drugs”, al-Farabi ave., 75a, Almaty, 050060, Kazakhstan

R.A. Parenova

JSC “Scientific Center of Anti-Infectious Drugs”, al-Farabi ave., 75a, Almaty, 050060, Kazakhstan

T.Kh. Izmailov

LLP “Research and Production Association Kazpharmacom”, Khmeleva str., 1/13, Almaty, 050010, Kazakhstan


Outbreaks of nosocomial infections strike the public health system around the world. Current surveillance systems for infectious agents either take too long to identify pathogens or lack the necessary sensitivity to distinguish the virulent strains from the benign ones in the resident microflora. To address this problem, we propose a method for improving the sensitivity and specificity of detection of virulent clonal lines of bacteria or individual virulence plasmids in metagenomic samples. In this study, we used previously developed computational tools, Barcode Generator and Barcoding 2.0, to analyse gut microflora of laboratory mice infected with a pathogenic multidrug-resistant S. aureus and treated with cefazolin, an iodine-containing complex CC-195, and by a combinatorial treatment. We searched the metagenomic samples for representatives of pathogenic microflora using diagnostic genetic barcodes, which were designed based on the whole genome sequences of a collection of clinical isolates. Our results demonstrated a practical applicability of these diagnostic barcodes to monitor clonal lines of pathogens and even individual virulence plasmids in the environment. We also found that the novel drug CC-195 promotes a speedy restoration of the normal gut microflora disturbed by infection and administration of the antibiotic cefazolin.


hospital infection, NGS sequencing, metagenome, diagnostics, DNA barcode, gut microflora

Article Details


Marcus S.L., Brumell J.H., Pfeifer C.G., Finlay B.B.. Salmonella pathogenicity islands: big virulence in small packages //Microbes and Infection. – 2000. – Vol. 2, No 2. – P. 145-156. PMID: 10742687. doi: 10.1016/s1286-4579(00)00273-2.

Cole J.R., Wang Q., Fish J.A., Chai B., McGarrell D.M., Sun Y., Brown C.T., Porras-Alfaro A., Kuske C.R.,. Tiedje J.M. Ribosomal Database Project: data and tools for high throughput rRNA analysis // Nucl. Acids Res. – 2014. – Vol. 42, No D1. – P. D633-D642. PMID: 24288368. doi: 10.1093/nar/gkt1244.

McDonald D., Price M.N., Goodrich J., Nawrocki E.P., DeSantis T.Z., Probst A., Andersen G.L., Knight R., Hugenholtz P. An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea // ISME J. – 2012. – Vol. 6, No 3. – P. 610-618. PMID: 22134646. doi: 10.1038/ismej.2011.139.

Wood D.E., Salzberg S.L. Kraken: ultrafast metagenomic sequence classification using exact alignments // Genome Biol. – 2014. – Vol. 15, No 3. – P. R46. PMID: 24580807/ doi: 10.1186/gb-2014-15-3-r46.

Menzel P., Kim Lee Ng., Krogh A. Fast and sensitive taxonomic classification for metagenomics with Kaiju // Nat. Commun. – 2016. – Vol. 7. – P. 11257. PMID: 27071849. doi: 10.1038/ncomms11257

Gaytan A., Bergsten J., Canelo T., Perez-Izquierdo C., Santoro M., Bonal R. DNA Barcoding and geographical scale effect: The problems of undersampling genetic diversity hotspots // Ecol. Evol. – 2020. – Vol. 10, No 19. – P. 10754-10772. PMID: 33072294. doi: 10.1002/ece3.6733.

Papaiakovou M., Littlewood D.T.J., Doyle S.R., Gasser R.B., Cantacessi C. Worms and bugs of the gut: the search for diagnostic signatures using barcoding, and metagenomics–metabolomics // Parasites Vectors. – 2022. – Vol. 15, No 1. – P. 118. PMID: 35365192. doi: 10.1186/s13071-022-05225-7.

Rotimi A.M., Pierneef R., Reva O.N. Selection of marker genes for genetic barcoding of microorganisms and binning of metagenomic reads by Barcoder software tools // BMC Bioinformatics. – 2018. – Vol. 19, No 1. – P. 309. PMID: 30165813. doi: 10.1186/s12859-018-2320-1.

Rose R., Golosova O., Sukhomlinov D., Tiunov A., Prosperi M. Flexible design of multiple metagenomics classification pipelines with UGENE // Bioinformatics. – 2019. – Vol. 35, No 11. – P. 1963-1965. PMID: 30358807. doi: 10.1093/bioinformatics/bty901.

Korotetskiy I.S., Jumagaziyeva A.B., Kerimzhanova B., Reva O.N., Shilov S.V., Kuznetsova T., Ivanova L., Korotetskaya N., Bekmukhamedova A., Satylgankyzy G., Klivleyeva N.G. Complete genome sequences of Gram-positive opportunistic pathogens isolated from hospitals in Almaty, Kazakhstan //. Microbiol Resour Announc. – 2022. – Vol. 11, No 4. – P. e00093-22. PMID: 35286173. doi: 10.1128/mra.00093-22.

Korotetskiy I., Jumagaziyeva A., Kerimzhanova B., Reva O., Kuznetsova T., Shilov S., Ivanova L., Zubenko N., Parenova R., Iskakbayeva Z., Baimakhanov B., Bekmuhamedova A. Whole genome sequence data of Stenotrophomonas maltophilia SCAID WND1-2022 (370) // Data Brief. – 2022. – Vol. 45. – P. 108694. PMID: 36425995. doi: 10.1016/j.dib.2022.108694.

Korotetskiy I.S., Shilov S.V., Kuznetsova T., Kerimzhanova B., Korotetskaya N., Ivanova L., Zubenko N., Parenova R., Reva O.N. Analysis of Whole-Genome Sequences of Pathogenic Gram-Positive and Gram-Negative Isolates from the Same Hospital Environment to Investigate Common Evolutionary Trends Associated with Horizontal Gene Exchange, Mutations and DNA Methylation Patterning // Microorganisms. – 2023. – Vol. 11, No 2. – P. 323. PMID: 36838287. doi: 10.3390/microorganisms11020323.