Abstract
Bacteriophage has become an attractive alternative for the treatment of antibiotic-resistant Staphylococcus aureus. For the success of phage therapy, phage host range is an important criterion when considering a candidate phage. Most reviews of S. aureus (SA) phages have focused on their impact on host evolution, especially their contribution to the spread of virulence genes and pathogenesis factors. The potential therapeutic use of SA phages, especially detailed characterizations of host recognition mechanisms, has not been extensively reviewed so far. In this report, we provide updates on the study of SA phages, focusing on host recognition mechanisms with the recent discovery of phage receptor-binding proteins (RBPs) and the possible applications of SA phages in phage therapy.
Similar content being viewed by others
References
Abedon ST, Kuhl SJ, Blasdel BG, Kutter EM (2011) Phage treatment of human infections. Bacteriophage 1:66–85. https://doi.org/10.4161/bact.1.2.15845
Ajuebor J, Buttimer C, Arroyo-Moreno S, Chanishvili N, Gabriel E, O’Mahony J, McAuliffe O, Neve H, Franz C, Coffey A (2018) Comparison of Staphylococcus phage K with close phage relatives commonly employed in phage therapeutics. Antibiotics 7:37. https://doi.org/10.3390/antibiotics7020037
Alves DR, Gaudion A, Bean JE, Perez Esteban P, Arnot TC, Harper DR, Kot W, Hansen LH, Enright MC, Jenkins ATA (2014) Combined use of bacteriophage K and a novel bacteriophage to reduce Staphylococcus aureus biofilm formation. Appl Environ Microbiol 80:6694–6703. https://doi.org/10.1128/AEM.01789-14
Azam AH (2019) Analysis of phage resistance mechanism of Staphylococcus aureus SA003 which causes bovine mastitis against phages ɸSA012 and ɸSA039. Dissertation, Tokyo Institute of Technology
Azam AH, Tanji Y (2019) Bacteriophage-host arm race: an update on the mechanism of phage resistance in bacteria and revenge of the phage with the perspective for phage therapy. Appl Microbiol Biotechnol 103(5):2121–2131. https://doi.org/10.1007/s00253-019-09629-x
Azam AH, Hoshiga F, Takeuchi I, Miyanaga K, Tanji Y (2018) Analysis of phage resistance in Staphylococcus aureus SA003 reveals different binding mechanisms for the closely related Twort-like phages ɸSA012 and ɸSA039. Appl Microbiol Biotechnol 102(20):8963–8977
Brown S, Xia G, Luhachack LG, Campbell J, Meredith TC, Chen C, Winstel V, Gekeler C, Irazoqui JE, Peschel A, Walker S (2012) Methicillin resistance in Staphylococcus aureus requires glycosylated wall teichoic acids. Proc Natl Acad Sci 109:18909–18914. https://doi.org/10.1073/pnas.1209126109
Brown S, Santa Maria JP, Walker S (2013) Wall teichoic acids of Gram-positive bacteria. Annu Rev Microbiol 67:313–336. https://doi.org/10.1146/annurev-micro-092412-155620
Brussow H, Canchaya C, Hardt W-D (2004) Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol Mol Biol Rev 68:560–602. https://doi.org/10.1128/MMBR.68.3.560-602.2004
Capparelli R, Parlato M, Borriello G, Salvatore P, Iannelli D (2007) Experimental phage therapy against Staphylococcus aureus in mice. Antimicrob Agents Chemother 51:2765–2773. https://doi.org/10.1128/aac.01513-06
Chan BK, Abedon ST, Loc-Carrillo C (2013) Phage cocktails and the future of phage therapy. Future Microbiol 8:769–783
Cui Z, Song Z, Wang Y, Zeng L, Shen W, Wang Z, Li Q, He P, Qin J, Guo X (2012) Complete genome sequence of wide-host-range Staphylococcus aureus phage JD007. J Virol 86:13880–13881. https://doi.org/10.1128/JVI.02728-12
Cui Z, Guo X, Dong K, Zhang Y, Li Q, Zhu Y, Zeng L, Tang R, Li L (2017) Safety assessment of Staphylococcus phages of the family Myoviridae based on complete genome sequences. Sci Rep 7:41259. https://doi.org/10.1038/srep41259
Deghorain M, Van Melderen L (2012) The staphylococci phages family: an overview. Viruses 4:3316–3335
Dunne M, Hupfeld M, Klumpp J, Loessner MJ (2018) Molecular basis of bacterial host interactions by Gram-positive targeting bacteriophages. Viruses 10:8
Dvořáčková M, Růžička F, Benešík M, Pantůček R, Dvořáková-Heroldová M (2018) Antimicrobial effect of commercial phage preparation Stafal® on biofilm and planktonic forms of methicillin-resistant Staphylococcus aureus. Folia Microbiol 64:121–126. https://doi.org/10.1007/s12223-018-0622-3
El Haddad L, Ben AN, Plante PL, Dumaresq J, Katsarava R, Labrie S, Corbeil J, St-Gelais D, Moineau S (2014) Improving the safety of Staphylococcus aureus polyvalent phages by their production on a Staphylococcus xylosus strain. PLoS One 9:7. https://doi.org/10.1371/journal.pone.0102600
Enault F, Briet A, Bouteille L, Roux S, Sullivan MB, Petit MA (2017) Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses. ISME J 11:237–247. https://doi.org/10.1038/ismej.2016.90
Endl J, Seidl HP, Fiedler F, Schleifer KH (1983) Chemical composition and structure of cell wall teichoic acids of staphylococci. Arch Microbiol 135:215–223. https://doi.org/10.1007/BF00414483
Enright MC, Robinson DA, Randle G, Feil EJ, Grundmann H, Spratt BG, Walsh CT (2002) The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc Natl Acad Sci 99:7687–7692
Feil EJ, Cooper JE, Grundmann H, Robinson DA, Enright MC, Berendt T, Peacock SJ, Smith JM, Murphy M, Spratt BG, Moore CE, Day NPJ (2003) How clonal is Staphylococcus aureus? J Bacteriol 185:3307–3316. https://doi.org/10.1128/JB.185.11.3307-3316.2003
Fischetti VA (2010) Bacteriophage endolysins: a novel anti-infective to control Gram-positive pathogens. Int J Med Microbiol 300:357–362
Fish R, Kutter E, Wheat G, Blasdel B, Kutateladze M, Kuhl S (2016) Bacteriophage treatment of intransigent diabetic toe ulcers: a case series. J Wound Care 25:S27–S33. https://doi.org/10.12968/jowc.2016.25.7.S27
Fujiki J, Nakamura T, Furusawa T, Ohno H, Takahashi H, Kitana J, Usui M, Higuchi H, Tanji Y, Tamura Y, Iwano H (2018) Characterization of the lytic capability of a lysk-like endolysin, lys-phiSA012, derived from a polyvalent Staphylococcus aureus bacteriophage. Pharmaceuticals 11(1). https://doi.org/10.3390/ph11010025
García P, Martínez B, Obeso JM, Lavigne R, Lurz R, Rodríguez A (2009) Functional genomic analysis of two Staphylococcus aureus phages isolated from the dairy environment. Appl Environ Microbiol 75:7663–7673. https://doi.org/10.1128/AEM.01864-09
Gerlach D, Guo Y, De Castro C, Kim S-H, Schlatterer K, Xu F-F, Pereira C, Seeberger PH, Ali S, Codée J, Sirisarn W, Schulte B, Wolz C, Larsen J, Molinaro A, Lee BL, Xia G, Stehle T, Peschel A (2018) Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity. Nature 563:705–709. https://doi.org/10.1038/s41586-018-0730-x
Hsieh SE, Lo HH, Chen ST, Lee MC, Tseng YH (2011) Wide host range and strong lytic activity of Staphylococcus aureus lytic phage Stau2. Appl Environ Microbiol 77:756–761. https://doi.org/10.1128/AEM.01848-10
Iwano H, Inoue Y, Takasago T, Kobayashi H, Furusawa T, Taniguchi K, Fujiki J, Yokota H, Usui M, Tanji Y, Hagiwara K, Higuchi H, Tamura Y (2018) Bacteriophage ΦSA012 has a broad host range against Staphylococcus aureus and effective lytic capacity in a mouse mastitis model. Biology 7:8. https://doi.org/10.3390/biology7010008
Jikia D, Chkhaidze N, Imedashvili E, Mgaloblishvili I, Tsitlanadze G, Katsarava R, Morris JG, Sulakvelidze A (2005) The use of a novel biodegradable preparation capable of the sustained release of bacteriophages and ciprofloxacin, in the complex treatment of multidrug-resistant Staphylococcus aureus-infected local radiation injuries caused by exposure to Sr90. Clin Exp Dermatol 30:23–26. https://doi.org/10.1111/j.1365-2230.2004.01600.x
Kaneko J, Narita-Yamada S, Wakabayashi Y, Kamio Y (2009) Identification of ORF636 in phage φSLT carrying Panton-Valentine leukocidin genes, acting as an adhesion protein for a poly(glycerophosphate) chain of lipoteichoic acid on the cell surface of Staphylococcus aureus. J Bacteriol 191:4674–4680. https://doi.org/10.1128/JB.01793-08
Khairullin IN, Pozdeev OK, Shaimordanov R (2002) Efficiency of using specific bacteriophages in the treatment and prophylaxis of surgical postoperative infections. Kazan Med J 83:258–261 [Article in Russian]
Kloos WE, Bannerman TL (1994) Update on clinical significance of coagulase-negative staphylococci. Clin Microbiol Rev 7:117–140
Kumaran D, Taha M, Yi QL, Ramirez-Arcos S, Diallo JS, Carli A, Abdelbary H (2018) Does treatment order matter? Investigating the ability of bacteriophage to augment antibiotic activity against Staphylococcus aureus biofilms. Front Microbiol 9:127. https://doi.org/10.3389/fmicb.2018.00127
Kvachadze L, Balarjishvili N, Meskhi T, Tevdoradze E, Skhirtladze N, Pataridze T, Adamia R, Topuria T, Kutter E, Rohde C, Kutateladze M (2011) Evaluation of lytic activity of staphylococcal bacteriophage Sb-1 against freshly isolated clinical pathogens. Microb Biotechnol 4:643–650. https://doi.org/10.1111/j.1751-7915.2011.00259.x
Kwan T, Liu J, DuBow M, Gros P, Pelletier J (2005) The complete genomes and proteomes of 27 Staphylococcus aureus bacteriophages. Proc Natl Acad Sci 102:5174–5179. https://doi.org/10.1073/pnas.0501140102
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. https://doi.org/10.3390/v9090258
Li X, Gerlach D, Du X, Larsen J, Stegger M, Kuhner P, Peschel A, Xia G, Winstel V (2015) An accessory wall teichoic acid glycosyltransferase protects Staphylococcus aureus from the lytic activity of Podoviridae. Sci Rep 5:17219. https://doi.org/10.1038/srep17219
Li X, Koç C, Kühner P, Stierhof Y-D, Krismer B, Enright MC, Penadés JR, Wolz C, Stehle T, Cambillau C, Peschel A, Xia G (2016) An essential role for the baseplate protein Gp45 in phage adsorption to Staphylococcus aureus. Nat Publ Gr 6:26455. https://doi.org/10.1038/srep26455
Lindsay JA (2010) Genomic variation and evolution of Staphylococcus aureus. Int J Med Microbiol 300:98–103
Liu J, Dehbi M, Moeck G, Arhin F, Bauda P, Bergeron D, Callejo M, Ferretti V, Ha N, Kwan T, McCarty J, Srikumar R, William D, Wu JJ, Gros P, Pelletier J, Dubow M (2004) Antimicrobial drug discovery through bacteriophage genomics. Nat Biotechnol 22:185–191
Lobocka M, Hejnowicz MS, Dabrowski K, Gozdek A, Kosakowski J, Witkowska M, Ulatowska MI, Weber-Dabrowska B, Kwiatek M, Parasion S, Gawor J, Kosowska H, Glowacka A (2012) Genomics of staphylococcal Twort-like phages potential therapeutics of the post-antibiotic era. Adv Virus Res 83:143–216. https://doi.org/10.1016/B978-0-12-394438-2.00005-0
Maciejewska B, Olszak T, Drulis-Kawa Z (2018) Applications of bacteriophages versus phage enzymes to combat and cure bacterial infections: an ambitious and also a realistic application? Appl Microbiol Biotechnol 102:2563–2581
Martínez-Rubio R, Quiles-Puchalt N, Martí M, Humphrey S, Ram G, Smyth D, Chen J, Novick RP, Penadés JR (2017) Phage-inducible islands in the Gram-positive cocci. ISME J 11:1029–1042. https://doi.org/10.1038/ismej.2016.163
Matsuzaki S, Yasuda M, Nishikawa H, Kuroda M, Ujihara T, Shuin T, Shen Y, Jin Z, Fujimoto S, Nasimuzzaman MD, Wakiguchi H, Sugihara S, Sugiura T, Koda S, Muraoka A, Imai S (2003) Experimental protection of mice against lethal Staphylococcus aureus infection by novel bacteriophage φMR11. J Infect Dis 187:613–624. https://doi.org/10.1086/374001
McCallin S, Sarker SA, Sultana S, Oechslin F, Brüssow H (2018) Metagenome analysis of Russian and Georgian Pyophage cocktails and a placebo-controlled safety trial of single phage versus phage cocktail in healthy Staphylococcus aureus carriers. Environ Microbiol 20:3278–3293. https://doi.org/10.1111/1462-2920.14310
McCarthy AJ, Witney AA, Lindsay JA (2012) Staphylococcus aureus temperate bacteriophage: carriage and horizontal gene transfer is lineage associated. Front Cell Infect Microbiol 2:6. https://doi.org/10.3389/fcimb.2012.00006
Melo LDR, Brandão A, Akturk E, Santos SB, Azeredo J (2018) Characterization of a new Staphylococcus aureus Kayvirus harboring a lysin active against biofilms. Viruses 10:182. https://doi.org/10.3390/v10040182
Meredith TC, Swoboda JG, Walker S (2008) Late-stage polyribitol phosphate wall teichoic acid biosynthesis in Staphylococcus aureus. J Bacteriol 190:3046–3056. https://doi.org/10.1128/JB.01880-07
Moodley A, Kot W, Nälgård S, Jakociune D, Neve H, Hansen LH, Guardabassi L, Vogensen FK (2018) Isolation and characterization of bacteriophages active against methicillin-resistant Staphylococcus pseudintermedius. Res Vet Sci 122:81–85. https://doi.org/10.1016/j.rvsc.2018.11.008
Morozova VV, Vlassov VV, Tikunova NV (2018) Applications of bacteriophages in the treatment of localized infections in humans. Front Microbiol 9:1696
Nobrega FL, Vlot M, de Jonge PA, Dreesens LL, Beaumont HJE, Lavigne R, Dutilh BE, Brouns SJJ (2018) Targeting mechanisms of tailed bacteriophages. Nat Rev Microbiol 16:760–773. https://doi.org/10.1038/s41579-018-0070-8
O’Flaherty S, Coffey A, Edwards R, Meaney W, Fitzgerald GF, Ross RP (2004) Genome of staphylococcal phage K: a new lineage of Myoviridae infecting Gram-positive bacteria with a low G+C content. J Bacteriol 186:2862–2871. https://doi.org/10.1128/JB.186.9.2862-2871.2004
O’Flaherty S, Ross RP, Coffey A (2009) Bacteriophage and their lysins for elimination of infectious bacteria: review article. FEMS Microbiol Rev 33:801–819
Pantůček R, Doškař J, Růžičková V, Kašpárek P, Oráčová E, Kvardová V, Rosypal S (2004) Identification of bacteriophage types and their carriage in Staphylococcus aureus. Arch Virol 149:1689–1703. https://doi.org/10.1007/s00705-004-0335-6
Pincus NB, Reckhow JD, Saleem D, Jammeh ML, Datta SK, Myles IA (2015) Strain specific phage treatment for Staphylococcus aureus infection is influenced by host immunity and site of infection. PLoS One 10:1371. https://doi.org/10.1371/journal.pone.0124280
Pollackt JH, Neuhaus FC (1994) Changes in wall teichoic acid during the rod-sphere transition of Bacillus subtilis 168. J Bacteriol 176:7252–7259. https://doi.org/10.1128/jb.176.23.7252-7259.1994
Pompilio A, De Nicola S, Crocetta V, Guarnieri S, Savini V, Carretto E, Di Bonaventura G (2015) New insights in Staphylococcus pseudintermedius pathogenicity: antibiotic-resistant biofilm formation by a human wound-associated strain. BMC Microbiol 15:109. https://doi.org/10.1186/s12866-015-0449-x
Rashel M, Uchiyama J, Ujihara T, Uehara Y, Kuramoto S, Sugihara S, Yagyu K, Muraoka A, Sugai M, Hiramatsu K, Honke K, Matsuzaki S (2007) Efficient elimination of multidrug-resistant Staphylococcus aureus by cloned Lysin derived from bacteriophage φMR11. J Infect Dis 196:1237–1247. https://doi.org/10.1086/521305
Rippon JE (1956) The classification of bacteriophages lysing staphylococci. J Hyg 54:213–226. https://doi.org/10.1017/S0022172400044478
Sakoulas G, Eliopoulos GM, Fowler VG, Moellering RC, Novick RP, Lucindo N, Yeaman MR, Bayer AS (2005) Reduced susceptibility of Staphylococcus aureus to vancomycin and platelet microbicidal protein correlates with defective autolysis and loss of accessory gene regulator (agr) function. Antimicrob Agents Chemother 49:2687–2692. https://doi.org/10.1128/AAC.49.7.2687-2692.2005
Schmelcher M, Loessner MJ (2014) Application of bacteriophages for detection of foodborne pathogens. Bacteriophage 4:28137
Shaw DR, Chatterjee AN (1971) O-Acetyl groups as a component of the bacteriophage receptor on Staphylococcus aureus cell walls. J Bacteriol 108:584–585
Sunagar R, Patil SA, Chandrakanth RK (2010) Bacteriophage therapy for Staphylococcus aureus bacteremia in streptozotocin-induced diabetic mice. Res Microbiol 161:854–860. https://doi.org/10.1016/j.resmic.2010.09.011
Synnott AJ, Kuang Y, Kurimoto M, Yamamichi K, Iwano H, Tanji Y (2009) Isolation from sewage influent and characterization of novel Staphylococcus aureus bacteriophages with wide host ranges and potent lytic capabilities. Appl Environ Microbiol 75:4483–4490. https://doi.org/10.1128/AEM.02641-08
Takemura-Uchiyama I, Uchiyama J, ichiro KS, Inoue T, Ujihara T, Ohara N, Daibata M, Matsuzaki S (2013) Evaluating efficacy of bacteriophage therapy against Staphylococcus aureus infections using a silkworm larval infection model. FEMS Microbiol Lett 347:52–60
Takemura-Uchiyama I, Uchiyama J, Osanai M, Morimoto N, Asagiri T, Ujihara T, Daibata M, Sugiura T, Matsuzaki S (2014) Experimental phage therapy against lethal lung-derived septicemia caused by Staphylococcus aureus in mice. Microbes Infect 16:512–517. https://doi.org/10.1016/j.micinf.2014.02.011
Takeuchi I, Osada K, Azam AH, Asakawa H, Miyanaga K, Tanji Y (2016) The presence of two receptor-binding proteins contributes to the wide host range of staphylococcal Twort-like phages. Appl Environ Microbiol 82:5763–5774. https://doi.org/10.1128/AEM.01385-16
Tanji Y, Shimada T, Yoichi M, Miyanaga K, Hori K, Unno H (2004) Toward rational control of Escherichia coli O157:H7 by a phage cocktail. Appl Microbiol Biotechnol 64:270–274. https://doi.org/10.1007/s00253-003-1438-9
Tanji Y, Shimada T, Fukudomi H, Miyanaga K, Nakai Y, Unno H (2005) Therapeutic use of phage cocktail for controlling Escherichia coli O157:H7 in gastrointestinal tract of mice. J Biosci Bioeng 100:280–287. https://doi.org/10.1263/jbb.100.280
Tong SYC, Davis JS, Eichenberger E, Holland TL, Fowler VG (2015) Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 28:603–661. https://doi.org/10.1128/CMR.00134-14
Uchiyama J, Takemura-UchiyAma I, Kato SI, Sato M, Ujihara T, Matsui H, Hanaki H, Daibata M, Matsuzaki S (2014) In silico analysis of AHJD-like viruses, Staphylococcus aureus phages S24-1 and S13’, and study of phage S24-1 adsorption. MicrobiologyOpen 3:257–270. https://doi.org/10.1002/mbo3.166
Uchiyama J, Taniguchi M, Kurokawa K, Takemura-Uchiyama I, Ujihara T, Shimakura H, Sakaguchi Y, Murakami H, Sakaguchi M, Matsuzaki S (2017) Adsorption of Staphylococcus viruses S13′ and S24-1 on Staphylococcus aureus strains with different glycosidic linkage patterns of wall teichoic acids. J Gen Virol 98:2171–2180. https://doi.org/10.1099/jgv.0.000865
Utter B, Deutsch DR, Schuch R, Winer BY, Verratti K, Bishop-Lilly K, Sozhamannan S, Fischetti VA (2014) Beyond the chromosome: the prevalence of unique extra-chromosomal bacteriophages with integrated virulence genes in pathogenic Staphylococcus aureus. PLoS One 9:6. https://doi.org/10.1371/journal.pone.0100502
Vandersteegen K, Mattheus W, Ceyssens P-J, Bilocq F, De Vos D, Pirnay J-P, Noben J-P, Merabishvili M, Lipinska U, Hermans K, Lavigne R (2011) Microbiological and molecular assessment of bacteriophage ISP for the control of Staphylococcus aureus. PLoS One 6:24418. https://doi.org/10.1371/journal.pone.0024418
Winstel V, Liang C, Sanchez-Carballo P, Steglich M, Munar M, Broker BM, Penadés JR, Nübel U, Holst O, Dandekar T, Peschel A, Xia G (2013) Wall teichoic acid structure governs horizontal gene transfer between major bacterial pathogens. Nat Commun 4:2345. https://doi.org/10.1038/ncomms3345
Winstel V, Sanchez-Carballo P, Holst O, Xia G, Peschel A (2014) Biosynthesis of the unique wall teichoic acid of Staphylococcus aureus lineage ST395. MBio 5:2. https://doi.org/10.1128/mBio.00869-14
Xia G, Wolz C (2014) Phages of Staphylococcus aureus and their impact on host evolution. Infect Genet Evol 21:593–601. https://doi.org/10.1016/j.meegid.2013.04.022
Xia G, Maier L, Sanchez-Carballo P, Li M, Otto M, Holst O, Peschel A (2010) Glycosylation of wall teichoic acid in Staphylococcus aureus by TarM. J Biol Chem 285:13405–13415. https://doi.org/10.1074/jbc.M109.096172
Xia G, Corrigan RM, Winstel V, Goerke C, Gründling A, Peschel A (2011) Wall teichoic acid-dependent adsorption of staphylococcal siphovirus and myovirus. J Bacteriol 193:4006–4009. https://doi.org/10.1128/JB.01412-10
Acknowledgements
The first author would like to thank the Ministry of Education, Culture, Sports, Science and Technology of Japan for providing a scholarship during his doctoral study.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Ethical approval
This article does not contain any studies with human participants or animal performed by any of the authors.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Azam, A.H., Tanji, Y. Peculiarities of Staphylococcus aureus phages and their possible application in phage therapy. Appl Microbiol Biotechnol 103, 4279–4289 (2019). https://doi.org/10.1007/s00253-019-09810-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-019-09810-2