Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Antimicrobial Agents and Chemotherapy
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Mechanisms of Resistance

Molecular Characterization of rpoBMutations Conferring Cross-Resistance to Rifamycins on Methicillin-Resistant Staphylococcus aureus

Thomas A. Wichelhaus, Volker Schäfer, Volker Brade, Boris Böddinghaus
Thomas A. Wichelhaus
Institute of Medical Microbiology, University Hospital of Frankfurt, Frankfurt am Main, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Volker Schäfer
Institute of Medical Microbiology, University Hospital of Frankfurt, Frankfurt am Main, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Volker Brade
Institute of Medical Microbiology, University Hospital of Frankfurt, Frankfurt am Main, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Boris Böddinghaus
Institute of Medical Microbiology, University Hospital of Frankfurt, Frankfurt am Main, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/AAC.43.11.2813
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

Mutations of the rpoB gene conferring resistance to rifampin were analyzed in 40 methicillin-resistant Staphylococcus aureus isolates obtained from six countries. Interestingly, the majority of clinical isolates showed multiple mutations withinrpoB. The amino acid substitution 481His→Asn was the most prevalent one, capable of conferring low-level resistance on its own. Cross-resistance to rifampin, rifabutin, and rifapentine was demonstrated for all mutants identified. The level of resistance to rifamycins correlated with both the mutation position and type of amino acid substitution.

Multiresistance as a common feature in methicillin-resistant Staphylococcus aureus (MRSA) is a growing problem not only in hospital settings (5, 10, 22). Glycopeptides are the antibiotics of choice in the treatment of infections caused by MRSA (15). A combination therapy, however, with an antibiotic such as rifampin that reveals strong activity and good tissue penetration often is required to reach deep-seated infections effectively (6, 9, 16). Rifampin acts by inhibiting bacterial RNA polymerase (23). Previous studies on other bacteria provide evidence that mutations inrpoB, the gene which encodes the β subunit of RNA polymerase, are responsible for rifampin resistance (Rifr) (2, 8, 12, 17, 18, 20). By using pairs of isogenic S. aureus isolates gathered before and after acquisition of resistance under rifampin therapy, Aubry-Damon et al. recently demonstrated the occurrence of amino acid substitutions within a short conserved region of the β subunit and correlated the level of rifampin resistance with the mutations involved (2).

The present study was aimed at determining the distribution of mutations in the rpoB gene in clinical isolates of rifampin-resistant MRSA as well as correlating the MICs of rifampin, rifabutin, and rifapentine with the locations and nature of the amino acid substitutions.

A total of 35 Rifr MRSA clinical isolates and five in vitro mutants generated from two rifampin-susceptible (Rifs) epidemic MRSA strains were analyzed in this study. Fifteen of the Rifr MRSA isolates were furnished by laboratories in the United States, France, Italy, Poland, and Slovenia, whereas 20 of the Rifr initial isolates were obtained between 1993 and 1998 from German hospitals. All MRSA isolates were analyzed by pulsed-field gel electrophoresis as described previously (24). Resistance to rifampin (Sigma, Deisenhofen, Germany), rifabutin (Pharmacia-Upjohn, Milan, Italy), and rifapentine (Hoechst Marion Roussel, Kansas, Mo.) was determined by the agar dilution method with Mueller-Hinton agar (Oxoid, Basingstoke, England) with an inoculum of 104 CFU per spot. Two oligonucleotide primers (Life Technologies, Eggenstein, Germany), rpoB1 (5′-ACC GTC GTT TAC GTT CTG TA) and rpoB2 (5′-TCA GTG ATA GCA TGT GTA TC), were designed to amplify and sequence a 460-bp PCR fragment encompassing clusters I and II of the rifampin resistance mutation sites of the S. aureus rpoB gene (1). Amplification was performed on a Gene Amp PCR system 2400 (Perkin-Elmer, Weiterstadt, Germany) under standard conditions. Direct sequencing of purified PCR products was carried out by using a dye reaction terminator cycle sequencing kit (PE Applied Biosystems, Weiterstadt, Germany) according to the protocol described by the manufacturer. Amplified DNA was sequenced in both directions by using the 310 genetic analyzer (Perkin-Elmer).

All MRSA isolates were characterized with regard to their genotypes and the MICs of rifampin, rifabutin, and rifapentine as shown in Table1. Comparable MICs of rifampin and rifapentine could be demonstrated for all MRSA isolates, whereas the MICs of rifabutin generally were two to eight times lower. The degree of resistance allowed classification of the strains in the categories of low-level resistance (MICs, 1 to 4 μg/ml) and high-level resistance (MICs, ≥8 μg/ml). Restriction analysis of chromosomal DNA demonstrated the unrelatedness of the majority of isolates and revealed 19 different genotypes, with MRSA T38 and T23 representing the southern and northern German epidemic strains, respectively (Fig.1). Sequence analysis of 40 MRSA isolates from six countries revealed missense mutations in a short region of therpoB gene equivalent to clusters I and II ofEscherichia coli (18) (Fig.2). Twelve mutational changes at 10 positions were identified, with 473Ala→Thr representing a new mutation site. New amino acid substitutions, 465Gln→Arg, 466Leu→Ser, 468Gln→Lys, and 477Ala→Thr in cluster I and 527Ile→Met and 529Ser→Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions (2, 4, 7, 8, 18-21). Sequence findings allowed the categorization of all of the rifampin-resistant MRSA isolates into 12 different genotypes with respect to the mutations involved (Table2). Despite the different geographical origins of the isolates (Table 1), codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His→Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln→Lys also causes high-level resistance.

View this table:
  • View inline
  • View popup
Table 1.

Strain characterization

Fig. 1.
  • Open in new tab
  • Download powerpoint
Fig. 1.

Pulsed-field gel electrophoresis patterns ofSmaI digests of total DNA from representatives of each pulsotype (indicated by capital letters above lanes). Lanes m, size markers. Molecular sizes (in kilobases) are indicated on the right.

Fig. 2.
  • Open in new tab
  • Download powerpoint
Fig. 2.

Alignment of E. coli, Mycobacterium tuberculosis, and S. aureus rpoB sequences representing clusters I and II (1-3, 11, 14, 25, 26). The amino acid alignment is presented in a single-letter code. Asterisks symbolize identity to E. coli sequence. Positions involved in rifampin resistance are marked; mutations are indicated by downward-pointing arrows; insertions are indicated by upside-down triangles; and deletions are underlined. The new Rifr mutation site found in this study is indicated by a double downward-pointing arrow. Amino acid substitutions involved in Rifr found in this study are presented in italics. Amino acid substitutions not previously described are indicated in boldface.

View this table:
  • View inline
  • View popup
Table 2.

Correlation of mutations in the rpoB gene and the level of resistance to rifampin

Generation of Rifr mutants in vitro resulted in both of the phenotypes observed. Low-level resistance followed by a second mutation leading to high-level resistance also was demonstrated in vitro (Table2). Rifs strain T23 cultured on 0.0625 μg of rifampin-supplemented agar per ml revealed a new low-level resistant mutant with the amino acid substitution 471Asp→Tyr (T23a). When, in turn, T23a was plated on 64 μg of rifampin per ml, a new mutant readily acquired a second mutation, 486Ser→Leu, resulting in high-level resistance (T23aa). Rifs strain T38 was cultured on rifampin-supplemented agar at concentrations of 0.0625 and 64 μg/ml, and two single high-level resistance mutations were found with 468Gln→Lys (T38a) and 481His→Tyr (T38b), respectively. A substitution at amino acid position 481 within isolates T38b and T382 conferred low- or high-level resistance depending on the nature of the new amino acid (Table 2).

With respect to the pharmacokinetics of rifampin (27) and the findings presented in this study, we agree with the suggestion made by Aubry-Damon et al. (2) to revise the breakpoints for rifampin set by the National Committee for Clinical Laboratory Standards (13). Accordingly, new breakpoints of ≤0.5 and ≥8 μg/ml for the categorization of S. aureus relative to rifampin seem reasonable.

The goal of the present study was to elucidate the distribution of mutations within the rpoB gene in rifampin-resistant MRSA and to assess the in vitro effectiveness of different rifamycins against these isolates. By presenting seven new mutations, the study confirms that rpoB mutations are responsible for the common Rifr phenotype in MRSA and that the level of resistance to any rifamycin is dependent on both the type and the location of the mutation within the rpoB gene. The occurrence of multiple mutations within rpoB for S. aureus is first described in this study. Their presence might be explained by the epidemic nature of many MRSA strains and, consequently, the frequent exposure of these strains to rifampin chemotherapy. Finally, we were able to demonstrate that the mutations involved confer cross-resistance to rifampin, rifabutin, and rifapentine, thereby indicating that these antibiotics are likely to exhibit comparable effectiveness in the treatment of S. aureus infection.

ACKNOWLEDGMENTS

We thank Denia Franck and Michael Stappenbeck for their technical assistance as well as Sebastian Walpen for sequencing support.

FOOTNOTES

    • Received 1 February 1999.
    • Returned for modification 24 May 1999.
    • Accepted 25 August 1999.
  • Copyright © 1999 American Society for Microbiology

REFERENCES

  1. 1.↵
    1. Aboshkiwa M.,
    2. Rowland G.,
    3. Coleman G.
    Nucleotide sequence of the Staphylococcus aureus RNA polymerase rpoB gene and comparison of its predicted amino acid sequence with those of other bacteria. Biochim. Biophys. Acta 1262 1995 73 78
    OpenUrlPubMedWeb of Science
  2. 2.↵
    1. Aubry-Damon H.,
    2. Soussy C. J.,
    3. Courvalin P.
    Characterization of mutants in the rpoB gene that confer rifampin resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 42 1998 2590 2594
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    1. Bodmer T.,
    2. Zürcher G.,
    3. Imboden P.,
    4. Telenti A.
    Mutation position and type of substitution in the β-subunit of the RNA polymerase influence in-vitro activity of rifamycins in rifampicin-resistant Mycobacterium tuberculosis. J. Antimicrob. Chemother. 35 1995 345 348
    OpenUrlCrossRefPubMedWeb of Science
  4. 4.↵
    1. Carter P. E.,
    2. Abadi F. J. R.,
    3. Yakubu D. E.,
    4. Pennington T. H.
    Molecular characterization of rifampicin-resistant Neisseria meningitidis. Antimicrob. Agents Chemother. 38 1994 1256 1261
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Chambers H. F.
    Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications. Clin. Microbiol. Rev. 10 1997 781 791
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Fujii K.,
    2. Tsuji A.,
    3. Miyazaki S.,
    4. Yamaguchi K.,
    5. Goto S.
    In vitro and in vivo antibacterial activities of KRM-1648 and KRM-1657, new rifamycin derivatives. Antimicrob. Agents Chemother. 38 1994 1118 1122
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Honore N.,
    2. Cole S. T.
    Molecular basis of rifampin resistance in Mycobacterium leprae. Antimicrob. Agents Chemother. 37 1993 414 418
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. Jin D. J.,
    2. Gross C. A.
    Mapping and sequencing of mutations in the Escherichia coli rpoB gene that lead to rifampicin resistance. J. Mol. Biol. 202 1988 45 58
    OpenUrlCrossRefPubMedWeb of Science
  9. 9.↵
    1. Kunin C. M.
    Antimicrobial activity of rifabutin. Clin. Infect. Dis. 22 1996 S3 S14
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Michel M.,
    2. Gutmann L.
    Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci: therapeutic realities and possibilities. Lancet 349 1997 1901 1906
    OpenUrlCrossRefPubMedWeb of Science
  11. 11.↵
    1. Miller L. P.,
    2. Crawford J. T.,
    3. Shinnick T. M.
    The rpoB gene of Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 38 1994 805 811
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Morrow T. O.,
    2. Harmon S. A.
    Genetic analysis of Staphylococcus aureus RNA polymerase mutants. J. Bacteriol. 137 1979 374 383
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    National Committee for Clinical Laboratory Standards Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically 4th ed. 1997 Approved standard M7-A4. National Committee for Clinical Laboratory Standards, Wayne, Pa.
  14. 14.↵
    1. Ovchinnikov Y. A.,
    2. Monastyrskaya G. S.,
    3. Gubanov V. V.,
    4. Guryev S. O.,
    5. Chertov O. Y.,
    6. Modyanov N. N.,
    7. Grinkevich V. A.,
    8. Makarova I. A.,
    9. Marchenko T. V.,
    10. Polovnikova I. N.,
    11. Lipkin V. M.,
    12. Sverdlov E. D.
    The primary structure of Escherichia coli RNA polymerase. Eur. J. Biochem. 116 1981 621 629
    OpenUrlPubMedWeb of Science
  15. 15.↵
    1. Rahman M.
    Alternatives to vancomycin in treating methicillin-resistant Staphylococcus aureus infections. J. Antimicrob. Chemother. 41 1998 325 328
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    1. Schmitz F. J.,
    2. Jones M. E.
    Antibiotics for treatment of infections caused by MRSA and elimination of MRSA carriage. What are the choices? Int. J. Antimicrob. Agents 9 1997 1 19
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Severinov K.,
    2. Mustaev A.,
    3. Severinova E.,
    4. Kozlov M.,
    5. Darst S. A.,
    6. Goldfarb A.
    The β-subunit rif-cluster I is only angstroms away from the active center of Escherichia coli RNA polymerase. J. Biol. Chem. 270 1995 29428 29432
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Severinov K.,
    2. Soushko M.,
    3. Goldfarb A.,
    4. Nikiforov V.
    Rifampicin region revisited. J. Biol. Chem. 268 1993 14820 14825
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    1. Severinov K.,
    2. Soushko M.,
    3. Goldfarb A.,
    4. Nikiforov V.
    RifR mutations in the beginning of the Escherichia coli rpoB gene. Mol. Gen. Genet. 244 1994 120 126
    OpenUrlCrossRefPubMedWeb of Science
  20. 20.↵
    1. Taniguchi H.,
    2. Aramaki H.,
    3. Nikaido Y.,
    4. Mizuguchi Y.,
    5. Nakamura M.,
    6. Koga T.,
    7. Yoshida S.
    Rifampicin resistance and mutation of the rpoB gene in Mycobacterium tuberculosis. FEMS Microbiol. Lett. 144 1996 103 108
    OpenUrlCrossRefPubMedWeb of Science
  21. 21.↵
    1. Telenti A.,
    2. Imboden P.,
    3. Marchesi F.,
    4. Lowrie D.,
    5. Cole S.,
    6. Colston M. J.,
    7. Matter L.,
    8. Schopfer K.,
    9. Bodmer T.
    Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet 341 1993 647 650
    OpenUrlCrossRefPubMedWeb of Science
  22. 22.↵
    1. Voss A.,
    2. Milatovic D.,
    3. Wallrauch-Schwarz C.,
    4. Rosdahl V. T.,
    5. Braveny I.
    Methicillin-resistant Staphylococcus aureus in Europe. Eur. J. Clin. Microbiol. Infect. Dis. 13 1994 50 55
    OpenUrlCrossRefPubMedWeb of Science
  23. 23.↵
    1. Wehrli W.
    Rifampin: mechanisms of action and resistance. Rev. Infect. Dis. 5 1983 S407 S411
    OpenUrlCrossRefPubMedWeb of Science
  24. 24.↵
    1. Wichelhaus T. A.,
    2. Schulze J.,
    3. Hunfeld K. P.,
    4. Schäfer V.,
    5. Brade V.
    Clonal heterogeneity, distribution, and pathogenicity of methicillin-resistant Staphylococcus aureus. Eur. J. Clin. Microbiol. Infect. Dis. 16 1997 893 897
    OpenUrlCrossRefPubMedWeb of Science
  25. 25.↵
    1. Williams D. L.,
    2. Spring L.,
    3. Collins L.,
    4. Miller L. P.,
    5. Heifets L. B.,
    6. Gangadharam P. R. J.,
    7. Gillis T. P.
    Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 42 1998 1853 1857
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. Yang B.,
    2. Koga H.,
    3. Ohno H.,
    4. Ogawa K.,
    5. Fukuda M.,
    6. Hirakata Y.,
    7. Maesaki S.,
    8. Tomono K.,
    9. Tashiro T.,
    10. Kohno S.
    Relationship between antimycobacterial activities of rifampicin, rifabutin and KRM-1648 and rpoB mutations of Mycobacterium tuberculosis. J. Antimicrob. Chemother. 42 1998 621 628
    OpenUrlCrossRefPubMedWeb of Science
  27. 27.↵
    1. Yao J. D. C.,
    2. Moellering R. C.
    Antibacterial agents Manual of clinical microbiology 6th ed. Murray P. R., Baron E. J., Pfaller M. A., Tenover F. C., Yolken R. H. 1995 1281 1307 American Society for Microbiology Washington, D.C.
View Abstract
PreviousNext
Back to top
Download PDF
Citation Tools
Molecular Characterization of rpoBMutations Conferring Cross-Resistance to Rifamycins on Methicillin-Resistant Staphylococcus aureus
Thomas A. Wichelhaus, Volker Schäfer, Volker Brade, Boris Böddinghaus
Antimicrobial Agents and Chemotherapy Nov 1999, 43 (11) 2813-2816; DOI: 10.1128/AAC.43.11.2813

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Antimicrobial Agents and Chemotherapy article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Molecular Characterization of rpoBMutations Conferring Cross-Resistance to Rifamycins on Methicillin-Resistant Staphylococcus aureus
(Your Name) has forwarded a page to you from Antimicrobial Agents and Chemotherapy
(Your Name) thought you would be interested in this article in Antimicrobial Agents and Chemotherapy.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Molecular Characterization of rpoBMutations Conferring Cross-Resistance to Rifamycins on Methicillin-Resistant Staphylococcus aureus
Thomas A. Wichelhaus, Volker Schäfer, Volker Brade, Boris Böddinghaus
Antimicrobial Agents and Chemotherapy Nov 1999, 43 (11) 2813-2816; DOI: 10.1128/AAC.43.11.2813
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

Anti-Bacterial Agents
Plant Proteins
rifamycins
Staphylococcus aureus

Related Articles

Cited By...

About

  • About AAC
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • AAC Podcast
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #AACJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0066-4804; Online ISSN: 1098-6596