The Protection of Intracellular Brucella Against Therapeutic Agents and the Bactericidal Action of Serum

Shaffer, James M.; Kucera, C J; Spink, Wesley W.

doi:10.1084/jem.97.1.77

Cited by 85 publications

(26 citation statements)

References 14 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…More recently it has been well-documented that living intracellular bacteria are protected against the lethal action of antibiotics (1)(2)(3)(4)(5)(6). The mechanism whereby this occurs has been a subject of much discussion and investigation.…”

Section: Discussionmentioning

confidence: 99%

“…These studies suggest that a likely explanation for the survival of phagocytized bacteria in the presence of high concentrations of most antibiotics is the inability of the INTRODUCTION Several investigators have demonstrated that bacteria surviving intracellularly within phagocytes are not killed when incubated with concentrations of antibiotics many hundreds of times above the minimum bactericidal concentration (1)(2)(3)(4)(5)(6). Intraleukocytic bacteria may be unaffected by antibiotics because (a) the antibiotics do not reach the bacteria in their intracellular location or (b) the antibiotics do reach the bacteria, but because of altered metabolism, the bacteria are insensitive to the lethal action of the antibiotics.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Interaction of Intraleukocytic Bacteria and Antibiotics

Mandell¹

1973

J. Clin. Invest.

198

110

View full text Add to dashboard Cite

A B S T R A C T Bacteria that survive inside polymorphonuclear neutrophils (PMN) following phagocytosis are protected from the bactericidal action of most antibiotics. Two possible explanations are altered metabolism by intraleukocytic bacteria or failure of antibiotics to enter the phagosome. The oxygen consumption of intraleukocytic and extraleukocytic bacteria was measured as an index of bacterial metabolism. PMN respiration and bactericidal activity were suppressed with large doses of hydrocortisone and extraleukocytic bacterial oxygen consumption was abolished by the addition of lysostaphin. Intraleukocytic bacterial continued to consume oxygen suggesting that surviving ingested microorganisms are metabolically active. Neither penicillin (which cannot kill intraleukocytic bacteria) nor rifampin (which can kill intraleukocytic bacteria) was bactericidal for staphylococci at 5°C. Thus, rifampin is not uniquely able to kill "resting" bacteria. The total water space in the pellets was quantitated using tritium water and the extracellular water space was measured using Na2'5SO4. All penicillin associated with the cell pellet could be accounted for in extracellular water. Thus penicillin was completely excluded from the leukocytes. Rifampin was concentrated in the cell pellet 2.2 times when compared with the supernatant concentration.These studies suggest that a likely explanation for the survival of phagocytized bacteria in the presence of high concentrations of most antibiotics is the inability of the Dr. Mandell is the holder of a Research Career Development Award GM-49520 from the National Institute of General Medical Sciences.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Interaction of Intraleukocytic Bacteria and Antibiotics

Mandell¹

1973

J. Clin. Invest.

198

110

View full text Add to dashboard Cite

show abstract

“…Since aureomycin possesses antibacterial activity against a greater range of bacterial species than does penicillin, mice were treated with crystalline aureomycin prior to receiving Brucella endotoxin. Previous experiments had demonstrated that mice could be protected against viable Brucella by mixing the antibiotic with food (19). Therefore, a group of mice were fed with aureomycin for one week in a dose of 2.2 Gm.…”

Section: Resultsmentioning

confidence: 99%

Experimental Studies on the Significance of Endotoxin in the Pathogenesis of Brucellosis

Spink¹,

Anderson²

1954

J. Clin. Invest.

Self Cite

View full text Add to dashboard Cite

The participation of an endotoxin in the pathogenesis of brucellosis has received scant recognition although clinical observations have suggested that a Brucella toxin might be responsible for some of the manifestations in the acute phases of the disease. This has been especially obvious in patients whose illness has been due to Brucella melitensis. In general, brucellosis caused by Br. melitensis is a more severe disease than that resulting from Brucella abortus (1). It has also been observed in experimentally infected guinea pigs that Br. melitensis caused a more severe type of illness than did Br. abortus, although the abortus strains produced a larger number of demonstrable lesions in the tissues (2). Experience with aureomycin in the treatment of seriously ill patients with brucellosis has also suggested that an endotoxin might be responsible for some of the reactions observed after an initial dose of the antibiotic (3). Within eight to twelve hours after the first oral dose of aureomycin, an abrupt rise in temperature occurred, which was associated with a shock-like reaction, hypotension and tachycardia. Smaller initial doses of aureomycin eliminated the more severe reactions. A possible explanation for these clinical phenomena was that the antibrucella activity of the aureomycin resulted in the liberation of an agent or agents from the Brucella cells that provoked the undesired reactions. Further clinical observations that have promoted the present study were related to the dramatic improvement that occurred following the administration of adrenocorticotropin (4). No therapeutic agent available thus far for human brucellosis has resulted in a more rapid improvement in the condition of the acutely ill patient than that which has accompanied the use of either cortisone or adrenocorticotrophic hormone, even though the Brucella organisms have not been simultaneously eliminated from the tissues or blood stream. In view of the questions raised by these clinical observations, experiments were carried out to determine if the endotoxins of representative strains of the three species of Brucella differed in their toxicity for animals. The investigations were then extended to see if antibiotics or cortisone offered protection against the endotoxins. And finally, the acute lethal effect of the endotoxins was compared with that of living Brucella organisms.The concept that the endotoxin of Brucella organisms is related to the manifestations of the disease is in accord with many studies that have been carried out with the toxins of other gram-negative bacteria (5). It is now generally agreed that the endotoxins of gram-negative organisms are associated with somatic antigens located on or near the surface of smooth cultures of the cells (6). Little or none of the endotoxic substance is associated with the surface of rough colonies. These surface factors include the 0 and Vi antigens, and are composed of carbohydrate-lipoid-protein complexes, in which the carbohydrate is probably the major component (7).Miles and Pirie (...

show abstract

“…It was impossible, therefore, by the present method to assay other variables such as intracellular parasitism which conceivably might influence the antityphoidal activity of chlortetracycline and chloramphenicol in vivo. In studies with other microorganisms, however, the tetracycline drugs have been shown to be active in the same concentrations on bacteria situated within monocytes as on bacteria in the extracellular environment (18,19). Whether the other types of host cell parasitized by typhoid bacilli (e.g., plasma cells) (20) are as easily penetrated by the tetracyclines as the monocyte, has not yet been established.…”

Section: Discussionmentioning

confidence: 99%