Drug Resistance In Enterobacteriaceae Research Articles

Whole Genome Sequencing of Klebsiella pneumoniae Strain Unravels a New Model for the Development of Extensive Drug Resistance in Enterobacteriaceae.

Introduction:Increased incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been reported worldwide. The WHO warns about the imminent risk to global health if the spread of resistant bacteria is not contained.Materials and Methods:Here, single molecule real time sequencing was used to analyse the whole genome and resistome of SKGH01, a strain of Klebsiella pneumoniae.Results and Discussions:The data showed that SKGH01 was resistant to all commercially available antibiotics. A complete account of extensively drug-resistant (XDR) CRE at a genomic level and the entire location map of all antibiotic resistance components are here presented. Additionally, this work proposes a model of XDR acquisition in Enterobacteriaceae.

Genome-Wide Identification of Potential Drug Target in Enterobacteriaceae Family: A Homology-Based Method.

The Enterobacteriaceae is a large family of Gram-negative, facultative anaerobic, non-spore forming rod-shaped bacteria that includes harmless and pathogenic organisms. The emergence and development of drug resistance in Enterobacteriaceae is complicating the treatment of serious infections. The aim of this study is to predict and characterize putative drug targets in Enterobacteriaceae family employing a homology-based computational method. The final putative drug targets were qualitatively characterized via cellular function prediction, subcellular localization prediction, broad-spectrum, and druggability analyses. Of 6,327 analyzed proteins, 35 proteins were selected as final putative drug targets in Enterobacteriaceae family. These putative drug targets were involved in different vital pathways like metabolism, biosynthesis of macromolecule, and cell division. Predicted drug targets were also localized in the cytoplasm and cytoplasmic membrane of the pathogen that acts as antimicrobial or vaccine targets. Of 35 drug targets, 5 targets were druggable and 30 targets were not druggable and were predicted as novel drug targets, which should be further evaluated to develop new antimicrobial. Thirteen drug targets were considered as broad-spectrum targets. It is expected that results of our study could facilitate the production of novel antibacterial for efficient treatment of infections caused by Enterobacteriaceae pathogens.

Role of efflux pumps inhibitor in decreasing antibiotic resistance of Klebsiella pneumoniae in a tertiary hospital in North India.

The contribution of efflux systems to drug resistance in Enterobacteriaceae is becoming increasingly appreciated. This study phenotypically analyzed the role of efflux mechanisms in resistance to ertapenem, doripenem, and tigecycline among clinical isolates of carbapenem-resistant Klebsiella pneumoniae (CRKP). Multidrug-resistant and carbapenem non-susceptible K. pneumoniae isolates were determined by disk diffusion test. Further susceptibility of these isolates to carbapenems, ceftriaxone, cefoperazone, ceftazidime, tigecycline, and colistin was determined by agar dilution assay, and CRKP was identified. While modified Hodge test was used to confirm carbapenemase production, the contribution of efflux mechanisms was determined by a minimum inhibitory concentration (MIC) reduction assay, and typing was done by enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction (PCR). Of the 238 isolates of K. pneumoniae, 174 were multidrug resistant and 74 were CRKP. Forty of the CRKP were positive for carbapenemase production, while 43, 11, and 2 of the CRKP isolates had elevated MIC of ≥ 32 µg/mL for ertapenem, doripenem, and tigecycline, respectively. Twofold or higher MIC reduction to ertapenem, doripenem, and tigecycline was observed in 6, 28, and 27 isolates, respectively; however, non-susceptibility to ertapenem, doripenem and tigecycline was abolished in 2, 11, and 18 K. pneumoniae isolates, respectively. Nine clones of CRKP widely distributed within the hospital were obtained from ERIC PCR. Although colistin retained better activity against CRKP, efflux pumps contributed to increased MIC in ertapenem, doripenem, and tigecycline. Therefore, efflux systems are important aspects that should be explored in the fight against multidrug-resistant bacteria.

Antimicrobial Susceptibility and Multiplex PCR Screening of AmpC Genes From Isolates of Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens

The emergence of multiple drug resistance in Enterobacteriaceae is of particular concern. The aim of this study was to evaluate the antimicrobial susceptibility and screen for the ampC gene in three members of the Enterobacteriaceae family (Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens) found at Taichung Veterans General Hospital during the past 5 years using multiplex polymerase chain reaction (PCR). The susceptibility of thirty isolates from each of the three Enterobacteriaceae family members to five antimicrobial agents (ceftazidime, flomoxef, imipenem, moxifloxacin, and colistin) was assessed. The susceptibility was analyzed by disk diffusion, screening and confirmatory tests for extended-spectrum β-lactamases (ESBL) and minimum inhibitory concentration tests according to the recommendations of the Clinical and Laboratory Standards Institute. The detection of ampC genes (3 families, including DHA, EBC and CIT) was performed by multiplex PCR. To detect the coexistence of ESBL genes, PCR was performed using five primer pairs: TEM, SHV, SHV-5, CTX-M-3, and CTX-M-14. Of the 90 isolates, 53 (58.9%) were positive in the screening test for ESBL. Resistance genes were detected in 12 (22.6%) of these isolates: ampC gene of DHA type in one E. cloacae isolate and EBC type in three E. cloacae isolates; ampC gene of CIT type in four C. freundii isolates; CTX-M-3-like in one C. freundii isolate and one S. marcescens isolate; TEM in three E. cloacae isolates, three C. freundii isolates and two S. marcescens isolates; SHV in one C. freundii isolate. Antibiotic phenotypes cannot accurately distinguish the resistance mechanisms caused by ampC or ESBL, and especially in ESBL-ampC combinations. However, PCR is a useful technique for the identification of the different types of resistance genes.

Elimination of R-factor and inhibition of episomal drug resistance in enterobacteriaceae by antihistamines

Elimination of R-factor and inhibition of episomal drug resistance in enterobacteriaceae by antihistamines

Specific chromosomal affinity of a resistant factor.

SUMMARY R factors, responsible for transmissible drug resistance in Enterobacteriaceae, convert their hosts into donors of genetic material, but fewer recombinants for chromosomal genes are produced than with F. For one R factor, at least, this was merely a consequence of less frequent conjugation. With a mutant where conjugation was not repressed in contrast to the wild type, this R factor, R 1, was shown to behave like an F′ factor and to transfer the bacterial chromosome at high frequency from a fixed origin near the try genes.

Segregation during transfer of infectious drug resistance in Enterobacteriaceae.

MANY reports of infectious drug resistance suggest that all the resistance determinants of a multiple resistant donor strain are invariably transferred to the sensitive recipient strain.

Episome-mediated transfer of drug resistance in Enterobacteriaceae. IX. Recombination of an R factor with F.

Watanabe, Tsutomu (Keio University, Tokyo, Japan), and Chizuko Ogata. Episome-mediated transfer of drug resistance in Enterobacteriaceae. IX. Recombination of an R factor with F. J. Bacteriol. 91:43-50. 1966.-R factors can be transduced in Salmonella typhimurium with phage P-22, and a majority of the drug-resistant transductants are unable to transfer their drug resistance by cell-to-cell contact, as we have previously reported. Several exceptional types of transductants of S. typhimurium, with the markers of resistance to sulfonamide, streptomycin, and chloramphenicol, were recently obtained by transduction with phage P-22 of a four-drug-resistance R factor carrying the markers of resistance to sulfonamide, streptomycin, chloramphenicol, and tetracycline. They were exceptional in that they had low conjugal transferability of their drug resistance. When one of these exceptional transductants (38R) was transferred to an F(+) strain of Escherichia coli K-12, 38R acquired high transferability in its further transfer. This high transferability was found to be due to the recombination of 38R with F. Transductant 38R was of the fi(+) (fi = fertility inhibition) type, and did not show superinfection immunity against fi(+) and fi(-) R factors. The recombinant 38R.F was genetically very stable and resistant to elimination with acridines. It did not show superinfection immunity against fi(+) and fi(-) R factors, but did show superinfection immunity against F. Further, 38R.F did not restrict a female-specific phage (W-31), unlike wild-type F. F(-) and R(-) segregants were isolated from this recombinant 38R.F, and these segregants exhibited genetic characteristics different from the original R, its transductant 38R, and wild-type F.

Episome-mediated Transfer of Drug Resistance in Enterobacteriaceae X. Restriction and Modification of Phages by fi− R Factors

Watanabe, Tsutomu (Keio University, Tokyo, Japan), Toshiya Takano, Toshihiko Arai, Hiroshi Nishida, and Sachiko Sato. Episome-mediated transfer of drug resistance in Enterobacteriaceae. X. Restriction and modification of phages by fi(-) R factors. J. Bacteriol. 92:477-486. 1966.-An fi(-) R factor, which restricts phages lambda, T1, and T7 without modifying them, was found to restrict and not to modify an F(-)-specific phage, W-31, in Escherichia coli K-12, but not to restrict phage P-22 in Salmonella typhimurium LT-2, whereas other fi(-) R factors restricted and modified P-22 but not W-31; fi(+) R factors did not restrict these phages. Transduction and lysogenization with phages lambda and P-22 were reduced by these fi(-) R factors in K-12 and LT-2, respectively, and the transducing phages lambda and P-22 were modified by these fi(-) R factors. Spontaneous as well as ultraviolet-induced production of phage P-22 and zygotic induction of phage lambda were not significantly affected by any R factor. Injection of the nucleic acids of phages T1 and lambda was not affected by R factors, but the injected phage nucleic acids were rapidly broken down in the bacteria carrying fi(-) R factors. The nucleic acids of the modified phages were not broken down in these bacteria. It was assumed from these results that the mechanism of restriction of phages by fi(-) R factors is due to the breakdown of the injected phage nucleic acids by a deoxyribonuclease(s), presumably located near the cell surface in the cells carrying fi(-) R factors. The deoxyribonuclease(s), formed in the cells carrying the nonmodifying fi(-) R factor, is considered to be different from that synthesized in the cells carrying the modifying fi(-) R factors. It was further shown that the average burst sizes of the unmodified as well as modified phages are slightly reduced by the presence of the fi(-) R factors.

Effect of methylene blue on the action of 4-nitroquinoline N-oxide and acriflavine in inducing respiration-deficient mutants of Saccharomyces cerevisiae.

Japanese Journal of MicrobiologyVolume 9, Issue 3 p. 123-129 ArticleFree Access EFFECT OF METHYLENE BLUE ON THE ACTION OF 4-NITROQUINOLINE N-OXIDE AND ACRIFLAVINE IN INDUCING RESPIRATION-DEFICIENT MUTANTS OF SACCHAROMYCES CEREVISIAE Tamotsu Morita, Tamotsu Morita Department of Microbiology, Shizuoka College of Pharmacy, ShizuokaSearch for more papers by this authorIchiji Mifuchi, Ichiji Mifuchi Department of Microbiology, Shizuoka College of Pharmacy, ShizuokaSearch for more papers by this author Tamotsu Morita, Tamotsu Morita Department of Microbiology, Shizuoka College of Pharmacy, ShizuokaSearch for more papers by this authorIchiji Mifuchi, Ichiji Mifuchi Department of Microbiology, Shizuoka College of Pharmacy, ShizuokaSearch for more papers by this author First published: March 1965 https://doi.org/10.1111/j.1348-0421.1965.tb00281.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat REFERENCES 1Brenner, S., L. Barnett, F. H. C. Crick, and A. Orgel. 1961. The theory of mutagenesis. J. Mol. Biol. 3: 121. 2Ephrussi, B., P. L'Heritier et H. Hottinguer. 1949. Action de acriflavine sur les levures. VI. Analyse quantitative de la transformation des populations. Ann. inst. Pasteur 77: 64. 3Gause, G. G., N. P. Loshkareva, I. B. Zbarsky, and G. F. Gause. 1964. Deoxyribonucleic acid base composition in certain bacteria and their mutants with impaired respiration. Nature 203: 598. 4Hirota, Y. 1960. The effect of acridine dyes on mating type factors in Escherichia coli. Proc. Natl. Acad. Sci. U. S. 46: 57. 5Hirota, Y. and T. Iijima. 1957. Acriflavine as an effective agent for eliminating F-factor in Escherichia coli K-12. Nature 180: 655. 6Kotani, M., F. Egami, I. Watanabe, Y. Ikeda, and F. Osawa. 1963. Bunshiseibutsugaku. 2nd. ed. Asakura Shoten, Tokyo p. 48. (in Japanese). 7Lerman, L. S. 1961. Structural considerations in the interaction of deoxyribonucleic acid and acridines. J. Mol. Biol. 3: 18. 8Lindegren, C. C., S. Nagai, and H. Nagai. 1958. Induction of respiratory deficiency in yeast by manganese, copper, cobalt and nickel. Nature 182: 446. 9Mifuchi, I., and T. Morita. 1962. Induction of the respiration deficient mutant of Saccharomyces cerevisiae with carcinogenic agent, 4-nitroquinoline N-oxide. Medicine and Biology 64: 101. (in Japanese). 10Mifuchi, I., T. Morita, Y. Yanagihara, M. Hosoi, and M. Nishida. 1963. Induction of respiration-deficient mutant of Saccharomyces cerevisiae by carcinogenic agent, 4-nitroquinoline N-oxide and the existence of toxohormone-like factor in the mutant. Japan. J. Microbiol. 7: 69. 11Mitsuhashi, S., K. Harada, and M. Kameda. 1961. Elimination of transmissible drug-resistance by treatment with acriflavine. Nature 189: 947. 12Morita, T. Unpublished data. 13Nagai, S. 1959. Induction of the respiration deficient mutation in yeast by various synthetic dyes. Science 130: 1188. 14Nagai, S. 1962. Interferences between some inducers of the respiration-deficient mutation in yeast. Exptl. Cell Res. 24: 145. 15Nagai, S. 1963. Methylene blue and toluidine blue interfering with the production of respiration-deficient mutants in yeast by acriflavine. Exptl. Cell Res. 29: 82. 16Nagai, S. 1963. Spectrophotometry of yeast cell colored alive with acriflavine and other basic dyes. Exptl. Cell Res. 31: 275. 17Nagai, S., N. Yanagishima, and H. Nagai. 1961. Advances in the study of respiration-deficient (RD) mutation in yeast and other microorganisms. Bacteriol. Rev. 25: 404. 18Nagata, C., A. Imamura, K. Fukui, and H. Saito. 1963. Quantity of charge transfer and carcinogenic activity of 4-nitroquinoline 1-oxides and of some aromatic hydrocarbons. Gann 54: 401. 19Ogur, M., and R. S. John. 1956. A differential and diagnostic plating method for population studies of respiration deficieney in yeast. J. Bacteriol. 72: 500. 20Okabayashi, T. 1955. Studies on fungistatic substances (VIII). On the mutagenic activity of 4-nitroquinoline-1-oxide. J. Fer. Tech. 33: 513. (in Japanese). 21Okabayashi, T. 1962. Mutagenic activity of 4-hydroxyaminoquinoline 1-oxide. Chem. Pharm. Bull. 10: 1127. 22Ono, T. 1964. The effects of carcinogens on the biological activity of nucleic acids. Protein Nucleic Acid Enzyme 9: 1122. (in Japanese). 23Raut, C. 1953. A cytochrome deficient mutant of Saccharomyces cerevisiae. Exptl. Cell Res. 4: 295. 24Sugimura, T. Personal communication. 25Watanabe, T., and T. Fukusawa. 1961. Episome-mediated transfer of drug resistance in Enterobacteriaceae. II. Elimination of resistance factors with acridine dyes. J. Bacteriol. 81: 679. 26Yanagishima, N. 1956. On the W variant of yeast, with special reference to its appearance and character. J. Inst. Polytech. Osaka City Univ. Ser. D. 7: 131. 27Yas, M. 1956. A hereditary cytochrome-deficiency appearing in yeast grown at an elevated temperature. Exptl. Cell Res. 10: 746. Citing Literature Volume9, Issue3March 1965Pages 123-129 ReferencesRelatedInformation

EPISOME-MEDIATED TRANSFER OF DRUG RESISTANCE IN ENTEROBACTERIACEAE VIII

Watanabe, Tsutomu (Keio University School of Medicine, Tokyo, Japan), Chizuko Ogata, and Sachiko Sato. Episome-mediated transfer of drug resistance in Enterobacteriaceae. VIII. Six-drug-resistance R factor. J. Bacteriol. 88:922-928. 1964.-The multiple-drug-resistant Escherichia coli strain isolated by Lebek in 1963 was found to transfer resistance to sulfonamide, streptomycin, chloramphenicol, tetracycline, kanamycin, and neomycin together by conjugation, as well as by transduction with phage P1kc, suggesting that these drug-resistance markers are carried by a single R factor (R(6)). The results of transductional and spontaneous segregations of the drug-resistance markers of R(6) have shown that R(6) has independent genetic determinants for sulfonamide, streptomycin, chloramphenicol, tetracycline, and kanamycin-neomycin resistance. Resistance to kanamycin and neomycin is probably controlled by a single gene, because no segregation was observed between these two. The resistance transfer factor of R(6) was found to be of the fi(+) type.

EPISOME-MEDIATED TRANSFER OF DRUG RESISTANCE IN ENTEROBACTERIACEAE. VII. TWO TYPES OF NATURALLY OCCURRING R FACTORS.

Watanabe, Tsutomu (Keio University, Tokyo, Japan), Hiroshi Nishida, Chizuko Ogata, Toshihiko Arai, and Sachiko Sato. Episome-mediated transfer of drug resistance in Enterobacteriaceae. VII. Two types of naturally occurring R factors. J. Bacteriol. 88:716-726. 1964.-Naturally occurring R factors are classified into two types, fi(+) and fi(-), depending on their fi characters. The term fi is an abbreviation of fertility inhibition and fi(-) and fi(-) mean, respectively, the presence and absence of suppression of the functions of the sex factor F of Escherichia coli K-12. It was found that fi(-) R factors reduce the efficiency of plating of phages lambda and T(1) in K-12; fi(+) R factors did not have this inhibitory action. One of the fi(-) R factors reduced the efficiency of plating of phage T(7) as well. Phages lambda and T(1) underwent host-induced modifications in the host carrying some fi(-) R factors. At least two types of fi(-) R factors were recognized by the types of their restriction and host-induced modification of these phages. CaCl(2) exhibited antagonistic actions against the restrictions of phages lambda and T(1) by fi(-) R factors. Transduction of the ability to ferment galactose with HFT lysates of lambda was reduced by fi(-) R factors. Ultraviolet induction of lambda was not affected by any R factors. Furthermore, adsorption of phages lambda and T(1) was not altered by the presence of any R factors. From these results, we concluded that the suppression of progeny formation of these phages by fi(-) R factors is due to some step(s) after adsorption of the phages to the bacteria. Superinfection immunity and mutual exclusion were found between two different fi(+) R factors but not between fi(+) and fi(-) R factors. The two different fi(-) R factors were frequently genetically recombined. but fi(+) and fi(-) R factors were not genetically recombined, as indicated by findings of independent transfer of these R factors by conjugation and by transduction from the donors having these two R factors. It was assumed from these findings that fi(+) and fi(-) R factors are considerably different episomes having different resistance-transfer factors.

EPISOME-MEDIATED TRANSFER OF DRUG RESISTANCE IN ENTEROBACTERIACEAE. VI. HIGH-FREQUENCY RESISTANCE TRANSFER SYSTEM IN ESCHERICHIA COLI.

Watanabe, Tsutomu (Keio University, Tokyo, Japan). Episome-mediated transfer of drug resistance in Enterobacteriaceae. VI. High-frequency resistance transfer system in Escherichia coli. J. Bacteriol. 85:788-794. 1963.-R-factors (transmissible drug-resistance factors composed of the resistance-transfer factor and markers of resistance to sulfonamide, streptomycin, chloramphenicol, and tetracycline) gave rise to a high-frequency transfer system in Escherichia coli K-12 F(-), F(+), and Hfr strains that was similar to the high-frequency colicinogeny transfer system (HFCT) found by Stocker and Ozeki in Salmonella typhimurium with colicinogenic factor I. The procedure for obtaining a high-frequency transfer system of R-factors was identical to that for HFCT. The majority of cells of the high-frequency resistance transfer system were composed of cells which had just received R-factors by conjugation. These cells could act as highly competent donor cells for further transfer of the R-factors by conjugation. The frequencies of transfer of R-factors were as high as 1.5 to 7.5 per resistant donor cell introduced into mixed incubation with drug-sensitive recipient cells for 1 hr at 37 C, whereas the usual donor cells could transfer the R-factors at frequencies of, at most, 1:30 under similar conditions of mixed cultivation. It was also found that the aerobic conditions for growth of donor cells rather reduced the frequencies of transfer of R-factors in the usual systems. Possible mechanisms of the high-frequency resistance transfer system are discussed.

Episome-mediated transfer of drug resistance in Enterobacteriaceae. V. Spontaneous segregation and recombination of resistance factors in Salmonella typhimurium.

Watanabe, Tsutomu (Keio University, Tokyo, Japan) and Keong W. Lyang. Episomemediated transfer of drug resistance in Enterobacteriaceae. V. Spontaneous segregation and recombination of resistance factors in Salmonella typhimurium. J. Bacteriol. 84:422-430. 1962.-It was found that spontaneous segregation of the transmissible multiple drug resistance [resistance to streptomycin (Sm), chloramphenicol (Cm), tetracycline (TC), and sulfonamide (Su)] takes place so frequently in Salmonella typhimurium strain LT-2 (Su, Sm, Cm, Tc) as to allow a clone analysis of the segregation of resistance factors with replica plating. Su-, Sm-, and Cm- resistance factors together were spotaneously lost most frequently, whereas the spontaneous loss of Tc-resistance factor alone was rather infrequent. The complete loss of the resistance factors was also noted with low frequencies. The mechanism of the spontaneous segregation of the resistance factors was assumed to be due to either genetic exchange between the resistance factors and host genome or incomplete replication of the transmissible resistance factors (composed of resistance factors and resistance-transfer factor). In relation to the mechanism of spontaneous segregation of the transmissible resistance factors, circular models of the transmissible resistance factors are presented. Four-drug-resistant strains were produced by transferring segregant types of transmissible resistance factors (Su, Sm, Cm) and (Tc) to the strains with (Tc) and (Su, Sm, Cm), respectively. In these four-drug-resistant strains, the two types of transmissible resistance factors were found to be in two different states; in one state the two types of transmissible resistance factors exist in the same cells independently of each other, and in the other state a transmissible resistance factor, which was produced as a result of recombination of the two types of transmissible resistance factors, is present. Two unusual strains of LT-2 with Su-, Sm-, and Cm-resistance factors and with four resistance factors were found. These strains could not transfer their resistance factors to Escherichia coli K-12 by conjugation. Their resistance factors were spontaneously segregated as frequently as those of LT-2 (Su, Sm, Cm) and LT-2 (Su, Sm, Cm, Tc), and the transfer of (Tc) to strain LT-2 with nontransmissible Su-, Sm-, and Cm-resistance factors gave rise to two types of clones; one could transfer the four resistance factors as a unit to K-12 by conjugation, and another could transfer only (Tc) and frequently segregated two types of clones; one had (Tc) and another had nontransmissible Su, Sm-, and Cm-resistance factors. From these findings, the unusual strains with nontransmissible resistance factors are assumed to have a "defective" resistance-transfer factor.

Episome-mediated transfer of drug resistance in Enterobacteriaceae IV. Interactions between resistance transfer factor and F-factor in Escherichia coli K-12.

Watanabe, T. (Keio University, Tokyo, Japan) and T. Fukasawa. Episome-mediated transfer of drug resistance in Enterobacteriaceae. IV. Interactions between resistance transfer factor and F-factor in Escherichia coli K-12. J. Bacteriol. 83:727-735. 1962. - Resistance transfer factor (RTF) present in F(+) and F'(+) strains was found to suppress completely the transfer of F-factor, F', and host chromosomes. On the other hand, the presence of RTF in Hfr strains was found to reduce the frequencies of recombination to about 10(-2) of those in Hfr strains, regardless of the types of Hfr. RTF present in an F(+) strain with colicinogenic factor E(1) inhibited the transfer of the colicinogenic factor, whereas the transfer of colicinogenic factor I was not suppressed by RTF. A hypothesis that the genetic determinant of RTF controlling its "transfer system" is epistatic to that of F-factor is presented. It was also shown that F-factor present in recipients slightly suppresses the acceptance of RTF and that RTF present in recipients slightly reduces the acceptance of F-factor, F', and host chromosomes. On the other hand, the acceptance of RTF by recipients in which RTF is present was found to be about 1% of that in recipients without RTF.

Episome-mediated transfer of drug resistance in Enterobacteriaceae. III. Transduotion of resistance factors.

Watanabe, Tsutomu (Keio University, Tokyo, Japan), and Toshio Fukasawa. Episome-mediated transfer of drug resistance in Enterobacteriaceae. III. Transduction of resistance factors. J. Bacteriol. 82:202-209. 1961.-Transmissible multiple drug resistance of Enterobacteriaceae, which includes resistance to streptomycin (SM), chloramphenicol (CM), tetracycline (TC), and sulfonamide (Su), was found to be transduced in the systems of Salmonella typhimurium strain LT-2 with phage P-22 and Escherichia coli strain K-12 with phage P1kc. No linked chromosomal markers to the resistance factors have so far been found in the substrains of K-12. The transductants of K-12 were all found to be able to transfer their resistance factors by conjugation, whereas a majority of those of LT-2 could not transfer their resistance factors by conjugation. The resistance factors were segregated rarely in K-12 and consistently in LT-2. Defective resistance factors could be transferred by conjugation to the transductants of LT-2. The transductants thus made resistant to the four drugs were able to transfer only the resistance factors which had been introduced by conjugation and none of those which had been transduced. The patterns of segregation of the resistance factors by transduction suggested that they are located in the following sequence; Su-----Sm-----Cm-----Tc, and they were assumed to be carried by an episome "resistance transfer factor" which is considered to be located at the distal end of Tc.

“Resistance transfer factor” an episome in enterobacteriaceae

The transfer of multiple drug resistance in Enterobacteriaceae was studied by conjugation and transduction. The resistance factors were found to be carried by an episome (“resistance transfer factor (RTF)”).