History of the Streptothricin Antibiotics and Evidence for the Neglect of the Streptothricin Resistome

Overview

Journal NPJ Antimicrob Resist

Publisher Nature Portfolio

Date 2025 Jan 22

PMID 39843956

Authors

Ezabelle Franck

Terence S Crofts

Affiliations

Soon will be listed here.

Abstract

The streptothricin antibiotics were among the first antibiotics to be discovered from the environment and remain some of the most recovered antimicrobials in natural product screens. Increasing rates of antibiotic resistance and recognition that streptothricin antibiotics may play a role in countering so-called super-bugs has led to the re-evaluation of their clinical potential. Here we will review the current state of knowledge of streptothricins and their resistance in bacteria, with a focus on the potential for new resistance mechanisms and determinants to emerge in the context of potential widespread clinical adoption of this antibiotic class.

References

BORDERS D, SAX K, Lancaster J, HAUSMANN W, Mitscher L, Wetzel E . Structures of LL-AC541 and LL-AB664: new streptothricin-type antibiotics. Tetrahedron. 1970; 26(13):3123-33. DOI: 10.1016/s0040-4020(01)92895-9. View

Kim B, Lee J, Lee Y, Kim O, Chu J, Goo Y . N-methylstreptothricin D--a new streptothricin-group antibiotic from a Streptomyces spp. J Antibiot (Tokyo). 1994; 47(11):1333-6. DOI: 10.7164/antibiotics.47.1333. View

Haupt I, Hubener R, THRUM H . Streptothricin F, an inhibitor of protein synthesis with miscoding activity. J Antibiot (Tokyo). 1978; 31(11):1137-42. DOI: 10.7164/antibiotics.31.1137. View

Kusumoto S, Kambayashi Y, Imaoka S, Shima K, Shiba T . Total chemical structure of streptothricin. J Antibiot (Tokyo). 1982; 35(7):925-7. DOI: 10.7164/antibiotics.35.925. View

Inamori Y, Kato Y, Morimoto K, Morisaka K, Saito G, Sawada Y . Toxicological approaches to streptothricin antibiotics. III. Biological studies on delayed toxicity of streptothricin antibiotics in rats. Chem Pharm Bull (Tokyo). 1979; 27(11):2570-6. DOI: 10.1248/cpb.27.2570. View

Tietze E, Brevet J . Nucleotide sequence of the streptothricin-acetyl-transferase gene sat-2. Nucleic Acids Res. 1990; 18(5):1283. PMC: 330445. DOI: 10.1093/nar/18.5.1283. View

Wright G . The antibiotic resistome: the nexus of chemical and genetic diversity. Nat Rev Microbiol. 2007; 5(3):175-86. DOI: 10.1038/nrmicro1614. View

Tschape H, Tietze E, Prager R, Voigt W, Wolter E, SELTMANN G . Plasmid-borne streptothricin resistance in gram-negative bacteria. Plasmid. 1984; 12(3):189-96. DOI: 10.1016/0147-619x(84)90043-x. View

Burckhardt R, Escalante-Semerena J . Insights into the Function of the -Acetyltransferase SatA That Detoxifies Streptothricin in and . Appl Environ Microbiol. 2019; 85(6). PMC: 6414380. DOI: 10.1128/AEM.03029-18. View

10.

Gasparrini A, Markley J, Kumar H, Wang B, Fang L, Irum S . Tetracycline-inactivating enzymes from environmental, human commensal, and pathogenic bacteria cause broad-spectrum tetracycline resistance. Commun Biol. 2020; 3(1):241. PMC: 7229144. DOI: 10.1038/s42003-020-0966-5. View

11.

Wang Y, Chang C, Hsu N, Lo I, Lin K, Chen C . N-Formimidoylation/-iminoacetylation modification in aminoglycosides requires FAD-dependent and ligand-protein NOS bridge dual chemistry. Nat Commun. 2023; 14(1):2528. PMC: 10156733. DOI: 10.1038/s41467-023-38218-w. View

12.

Hamano Y, Matsuura N, Kitamura M, Takagi H . A novel enzyme conferring streptothricin resistance alters the toxicity of streptothricin D from broad-spectrum to bacteria-specific. J Biol Chem. 2006; 281(25):16842-16848. DOI: 10.1074/jbc.M602294200. View

13.

Moore I, Hughes D, Wright G . Tigecycline is modified by the flavin-dependent monooxygenase TetX. Biochemistry. 2005; 44(35):11829-35. DOI: 10.1021/bi0506066. View

14.

Benveniste R, Davies J . Aminoglycoside antibiotic-inactivating enzymes in actinomycetes similar to those present in clinical isolates of antibiotic-resistant bacteria. Proc Natl Acad Sci U S A. 1973; 70(8):2276-80. PMC: 433717. DOI: 10.1073/pnas.70.8.2276. View

15.

Haupt I, THRUM H . Bacterial resistance to streptothricins. J Basic Microbiol. 1985; 25(5):335-9. DOI: 10.1002/jobm.3620250508. View

16.

Kido Y, Furuie T, Suzuki K, Sakamoto K, Yokoyama Y, Uyeda M . A streptothricin-like antibiotic mixture, A-269A (and A-269A'). J Antibiot (Tokyo). 1987; 40(12):1698-706. DOI: 10.7164/antibiotics.40.1698. View

17.

Fernandez-Moreno M, Vallin C, Malpartida F . Streptothricin biosynthesis is catalyzed by enzymes related to nonribosomal peptide bond formation. J Bacteriol. 1997; 179(22):6929-36. PMC: 179630. DOI: 10.1128/jb.179.22.6929-6936.1997. View

18.

Payne D, Gwynn M, Holmes D, Pompliano D . Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov. 2006; 6(1):29-40. DOI: 10.1038/nrd2201. View

19.

Crofts T, Sontha P, King A, Wang B, Biddy B, Zanolli N . Discovery and Characterization of a Nitroreductase Capable of Conferring Bacterial Resistance to Chloramphenicol. Cell Chem Biol. 2019; 26(4):559-570.e6. PMC: 6474809. DOI: 10.1016/j.chembiol.2019.01.007. View

20.

Zahringer U, Voigt W, SELTMANN G . Nourseothricin (streptothricin) inactivated by a plasmid pIE636 encoded acetyl transferase of Escherichia coli: location of the acetyl group. FEMS Microbiol Lett. 1993; 110(3):331-4. DOI: 10.1111/j.1574-6968.1993.tb06344.x. View