• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of aacPermissionsJournals.ASM.orgJournalAAC ArticleJournal InfoAuthorsReviewers
Antimicrob Agents Chemother. Aug 1985; 28(2): 302–307.
PMCID: PMC180236

Evolution of plasmid-coded resistance to broad-spectrum cephalosporins.


A clinical isolate of Klebsiella ozaenae with transferable resistance to broad-spectrum cephalosporins produces a beta-lactamase determined by plasmid pBP60. The beta-lactamase had the same isoelectric point as SHV-1 (7.6). From heteroduplex analysis, an extensive homology between the two bla genes could be deduced; therefore, the new beta-lactamase was designated SHV-2. Enzymatic studies revealed that SHV-2 was able to hydrolyze broad-spectrum cephalosporins due to an increased affinity of these compounds for the enzyme. The assumption that SHV-2 is a natural mutant of SHV-1 was strongly supported by the isolation of a laboratory mutant of SHV-1 that showed activities similar to those of SHV-2.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bachmann BJ. Pedigrees of some mutant strains of Escherichia coli K-12. Bacteriol Rev. 1972 Dec;36(4):525–557. [PMC free article] [PubMed]
  • Chang AC, Cohen SN. Construction and characterization of amplifiable multicopy DNA cloning vehicles derived from the P15A cryptic miniplasmid. J Bacteriol. 1978 Jun;134(3):1141–1156. [PMC free article] [PubMed]
  • Fu KP, Neu HC. beta-lactamase stability of HR 756, a novel cephalosporin, compared to that of cefuroxime and cefoxitin. Antimicrob Agents Chemother. 1978 Sep;14(3):322–326. [PMC free article] [PubMed]
  • Grinsted J, Saunders JR, Ingram LC, Sykes RB, Richmond MH. Properties of a R factor which originated in Pseudomonas aeruginosa 1822. J Bacteriol. 1972 May;110(2):529–537. [PMC free article] [PubMed]
  • Hall A, Knowles JR. Directed selective pressure on a beta-lactamase to analyse molecular changes involved in development of enzyme function. Nature. 1976 Dec 23;264(5588):803–804. [PubMed]
  • Hedges RW, Datta N, Kontomichalou P, Smith JT. Molecular specificities of R factor-determined beta-lactamases: correlation with plasmid compatibility. J Bacteriol. 1974 Jan;117(1):56–62. [PMC free article] [PubMed]
  • Hirai K, Iyobe S, Inoue M, Mitsuhashi S. Purification and properties of a new beta-lactamase from Pseudomonas cepacia. Antimicrob Agents Chemother. 1980 Mar;17(3):355–358. [PMC free article] [PubMed]
  • Hirai K, Sato K, Matsubara N, Katsumata R, Inoue M, Mitsuhashi S. Immunological properties of beta-lactamases that hydrolyze cefuroxime and cefotaxime. Antimicrob Agents Chemother. 1981 Aug;20(2):262–264. [PMC free article] [PubMed]
  • Knothe H, Shah P, Krcmery V, Antal M, Mitsuhashi S. Transferable resistance to cefotaxime, cefoxitin, cefamandole and cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marcescens. Infection. 1983 Nov-Dec;11(6):315–317. [PubMed]
  • Labia R, Le Goffic F, Andrillon J. Etude cinétique de deux beta lactamases responsables d'un møeme phénotype. Biochimie. 1974;56(8):1025–1030. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Matthew M, Hedges RW, Smith JT. Types of beta-lactamase determined by plasmids in gram-negative bacteria. J Bacteriol. 1979 Jun;138(3):657–662. [PMC free article] [PubMed]
  • Meyer JF, Nies BA, Wiedemann B. Amikacin resistance mediated by multiresistance transposon Tn2424. J Bacteriol. 1983 Aug;155(2):755–760. [PMC free article] [PubMed]
  • Roupas A, Pitton JS. R factor-mediated and chromosomal resistance to ampicillin in Escherichia coli. Antimicrob Agents Chemother. 1974 Feb;5(2):186–191. [PMC free article] [PubMed]
  • Sanders CC, Sanders WE., Jr Emergence of resistance to cefamandole: possible role of cefoxitin-inducible beta-lactamases. Antimicrob Agents Chemother. 1979 Jun;15(6):792–797. [PMC free article] [PubMed]
  • Seeberg AH, Tolxdorff-Neutzling RM, Wiedemann B. Chromosomal beta-lactamases of Enterobacter cloacae are responsible for resistance to third-generation cephalosporins. Antimicrob Agents Chemother. 1983 Jun;23(6):918–925. [PMC free article] [PubMed]
  • Seibert G, Limbert M. Purification and characterization of a cephalosporinase from E. coli. Zentralbl Bakteriol Mikrobiol Hyg A. 1982 Dec;253(3):358–363. [PubMed]
  • Sykes RB, Nordström K. Microiodometric determination of beta-lactamase activity. Antimicrob Agents Chemother. 1972 Feb;1(2):94–99. [PMC free article] [PubMed]
  • Tajima M, Takenouchi Y, Sugawara S, Inoue M, Mitsuhashi S. Purification and properties of chromosomally mediated beta-lactamase from Citrobacter freundii GN7391. J Gen Microbiol. 1980 Dec;121(2):449–456. [PubMed]
  • van Treeck U, Schmidt F, Wiedemann B. Molecular nature of a streptomycin and sulfonamide resistance plasmid (pBP1) prevalent in clinical Escherichia coli strains and integration of an ampicillin resistance transposon (TnA). Antimicrob Agents Chemother. 1981 Mar;19(3):371–380. [PMC free article] [PubMed]
  • Vieira J, Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. [PubMed]
  • Vu H, Nikaido H. Role of beta-lactam hydrolysis in the mechanism of resistance of a beta-lactamase-constitutive Enterobacter cloacae strain to expanded-spectrum beta-lactams. Antimicrob Agents Chemother. 1985 Mar;27(3):393–398. [PMC free article] [PubMed]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...