The transfer of R factors in the human gastro-intestinal tract and the conditions under which it occurs was studied in healthy persons, who ingested derivatives of Escherichia coli containing chromosomal and R-factor-mediated resistance determinants that had been prepared from strains isolated from their own faeces. The experiments were designed to obtain presumptive evidence of survival and transfer of R factors by studying resistance-marker patterns of organisms isolated from the faeces. To prove conclusively that R-factor transfer had occurred and that the observed marker patterns were not fortuitous, studies of resistance-marker patterns in one of these subjects were supplemented by further detailed investigations including serological and molecular studies, which will be described in the succeeding paper.
An incidental finding was a significant positive correlation between the mean number of antibiotic-resistance determinants in resistant organisms and the age of an individual, although these studies were limited to a small and highly selected group of subjects.
No evidence of R-factor transfer was obtained in the absence of chemotherapy in four subjects, even though the plasmids concerned could be freely transferred in vitro from the potential donors to a wide range of faecal organisms, including the genetically marked ingested potential recipients. However, treatment of three subjects with a five-day course of a relevant antibiotic after ingestion of R factor bearing organisms led to the appearance in the faeces of large numbers of resistant coliform bacilli with antibiotic-resistance patterns consistent with transfer of the R factor either to an ingested potential recipient organism (one subject) or to endogenous strains of E. coli (two subjects).
Chemotherapy greatly prolonged the persistence of ingested R factors in the faecal flora long after the antibiotics were withdrawn and caused the number of R-factor bearing organisms in the faeces to increase. No evidence was obtained in limited studies of fragmentation or loss of R factors from ingested E. coli.
AndersonJ. D.,
GillespieW. A.,
RichmondM. H.1973a; The effect of antibiotics upon R-factor transfer between strains of Escherichia coli in the human gastro-intestinal tract. J. Med. Microbiol 6:ix
AndersonJ. D.,
IngramL. C.,
RichmondM. H.,
WiedemannB.1973b; Studies on the nature of plasmids arising from conjugation in the human gastro-intestinal tract. J. Med. Microbiol 6:475
AndersonJ. D.,
SykesR. B.1973; Characterisation of a β-lactamase obtained from a strain of Bacteroides fragilis resistant to β-lactam antibiotics. J. Med. Microbiol 6:201
BohušJ.1971; Acceptance of R factor by a Shigella sonnei strain from commensal Escherichia coli strains during dysentery. J. Hyg. Epidem. Microbiol. Immun 15:225
DaviesJoan R.,
FarrantW. N.,
TomlinsonA. J. H.1968; Further studies on the antibiotic resistance of Shigella sonnei. II. The acquisition of transferable antibiotic resistance in vivo. J. Hyg., Camb 66:479
DrasarB. S.,
ShinerMargot,
McLeodG. M.1969; Studies on the intestinal flora. I. The bacterial flora of the gastrointestinal tract in healthy and achlorhydric persons. Gastroenterology 56:71
FalkowS.,
HääpalaD. K.,
SilverR. P.1969; Relationships between extrachromo somal elements. In Bacterial episomes and plasmids edited by
WolstenholmeG. E. W.,
O’ConnorMaeve.
London: p 136
FarrarW. E.Jr,
EidsonMargene,
GuerryPatricia,
FalkowS.,
DrusinL. M.,
RobertsR. B.1972; Interbacterial transfer of R factor in the human intestine: in vivo acquisition of R-factor-mediated kanamycin resistance by a multiresistant strain of Shigella sonnei. J. Infect. Dis 126:27
GardnerP.,
SmithD. H.1969; Studies on the epidemiology of resistance (R) factors. I. Analysis of Klebsiella isolates in a general hospital. II. A prospective study of R factor transfer in the host. Ann. Intern. Med 71:1
GuinéeP. A. M.1965; Transfer of multiple drug resistance from Escherichia coli to Salmonella typhimurium in the mouse intestine. Antonie van Leeuwenhoek 31:314
SmithH. W.1969; Transfer of antibiotic resistance from animal and human strains of Escherichia coli to resident E. coli in the alimentary tract of man. Lancet 1:1174
WatanabeT.,
FukasawaT.1961; Episome-mediated transfer of drug resistance in Enterobacteriaceae. I. Transfer of resistance factors by conjugation. J. Bad 81:669
WiedemannB.1972; Resistance transfer in vivo and its inhibition. In Bacterial plasmids and antibiotic resistance. First International Symposium on Infectious Antibiotic Resistance. Smolenice, Czechoslovakia, 1971 Edited by
KrčméryV.,
RosivalL.,
WatanabeT.
Springer-Verlag, Berlin:75–91