June 25, 1999 

Introduction

Michael's Great Smokies lab reports of 8.7.98, 10.19.98, and 2.8.99 document
intestinal colonization by Klebsiella pneumoniae (Kp) and hemolytic Eschirichia
coli (hEc), which can translocate from gastrointestinal tissue into mesenteric
lymph nodes, peritoneum, and other tissues, including the brain.

The citations call attention to various aspects of Kp and hEc and, regarding
Michael, establish that translocation from gastrointestinal tissues can occur.

[a]  Probiotics can help diminish Kp (1).
[b]  Kp and Ec may work together and even share DNA material (2).
[c]  IFNg can augment toxicity to host (3).
[d]  Kp translocation hinted and/or documented (4, 5a-5d).
[e]  Hemmorhagic conditions augment bacterial translocation, suggesting a link
to hemolytic E. coli and its lysins, if co-colonized with Kp. Kp resisted one
experimental treatment (6).

[f]  Kp can translocate in human infants (7).
[g]  Case study. Liver abscess with Kp and Bd, plus meningitis and eye
involvment (8).
[h]  Gastrointestinal mucosal damage predisposes translocation of Kp and other
species (9).
[i]  Epithelial-attachment molecules are being delineated (eg, 10).
[j]  Antibiotic-resistant Kp and Ec (11).

[k]  Immunemodulators can assist anti-Kp pharmaceuticals (eg, 12).
[m]  Certain drugs can induce translocation (eg, 13).
[n]  Other toxins can augment translocation by Kp and other bacteria (14).
[o]  Mesenteric lymph nodes are a primary target for bacterial translocation,
including by Kp (15).
[p]  If systemic Kp and/or hEc fragments are reaching cells of the blood-brain
barrier, then vascular inflammation could be occurring (16a-b), along with
associated hypoperfusion and hypofuction in adjoining brain regions and neuronal
pathways connected thereto (17), as further delineated on a webpage
http://www.jorsm.com/~binstock/bbb-inf.htm

Teresa Binstock
Researcher in Developmental and Behavioral Neuroanatomy
June 25, 1999

 Summary Why Klebsiella pneumonia and hemolytic E. coli have come to demand much attention in this report. (Kp, hEc)

 Translocation of Kp and hEc

 Peritoneal and abdominal Kp and hEc

 Neurologic aspects of Kp and hEc

 Miscellany regarding Kp and hEc

 Additional tests

 Michael's index page

     A series of autism-spectrum research monographs is available by
     links on a web page: http://www.jorsm.com/~binstock/index.htm

1. J Pediatr Surg 1999 Feb;34(2):273-6 
Does probiotics administration decrease serum endotoxin levels in infants?
Urao M, Fujimoto T, Lane GJ, Seo G, Miyano T
Department of Pediatric Surgery, Juntendo University School of Medicine, Tokyo,
Japan.

PURPOSE: The aim of this study was to examine whether administration of
probiotics to infants can change the ratio of intestinal flora and thereby
decrease serum endotoxin produced by potentially pathogenic microorganisms.
METHODS: Nine infants including five with of biliary atresia, two with
omphalocele, one each with Hirschsprung's disease and imperforate anus were
studied. All patients were stable, and no antibiotics were given during this
study. A probiotic mixture consisting of Streptococcus faecalis, Clostridium
butyricum and Bacillus mesentericus was administered orally to each infant at
2g/day for 2 weeks. Fecal aerobic and anaerobic bacterial cultures, serum
endotoxin level, and other biochemical parameters were examined. RESULTS: In
fecal cultures, anaerobic bacteria including Bifidobacterium increased
significantly whereas Escherichia coli, Streptococcus, and Klebsiella tended to
decrease. The ratio of anaerobic to aerobic bacteria increased five times as a
result of administration of probiotics, and serum endotoxin levels decreased.
CONCLUSIONS: Probiotics affect intestinal bacterial flora by increasing
anaerobic bacteria and decreasing the population of potentially pathogenic
microorganisms. A decrease in luminal endotoxin may result in less endotoxin
translocation or bacterial translocation.
PMID: 10052803, UI: 99160168


2. J Bacteriol 1999 Apr;181(7):2307-13 
Conserved organization in the cps gene clusters for expression of Escherichia
coli group 1 K antigens: relationship to the colanic acid biosynthesis locus
and the cps genes from Klebsiella pneumoniae.
Rahn A, Drummelsmith J, Whitfield C
Department of Microbiology, The University of Guelph, Guelph, Ontario, Canada
N1G 2W1.

Group 1 capsules of Escherichia coli are similar to the capsules produced by
strains of Klebsiella spp. in terms of structure, genetics, and patterns of
expression. The striking similarities between the capsules of these organisms
prompted a more detailed investigation of the cps loci encoding group 1 capsule
synthesis. Six strains of K. pneumoniae and 12 strains of E. coli were
examined. PCR analysis showed that the clusters in these strains are conserved
in their chromosomal locations. A highly conserved block of four genes,
orfX-wza-wzb-wzc, was identified in all of the strains. The wza and wzc genes
are required for translocation and surface assembly of E. coli K30 antigen. The
conservation of these genes points to a common pathway for capsule
translocation. A characteristic JUMPstart sequence was identified upstream of
each cluster which may function in conjunction with RfaH to inhibit
transcriptional termination at a stem-loop structure found immediately
downstream of the "translocation-surface assembly" region of the cluster.
Interestingly, the sequence upstream of the cps clusters in five E. coli
strains and one Klebsiella strain indicated the presence of IS elements. We
propose that the IS elements were responsible for the transfer of the cps locus
between organisms and that they may continue to mediate recombination between
strains.
PMID: 10094716, UI: 99194747


3. Infect Immun 1998 Apr;66(4):1638-47 
Nuclear translocation of NF-kappaB in lipopolysaccharide-treated macrophages
fails to correspond to endotoxicity: evidence suggesting a requirement for a
gamma interferon-like signal.
Denlinger LC, Garis KA, Sommer JA, Guadarrama AG, Proctor RA, Bertics PJ
Department of Medical Microbiology and Immunology, University of Wisconsin
Medical School, Madison 53706, USA.

Elucidation of a signal transduction pathway essential to lipopolysaccharide
(LPS)-induced macrophage activation has the capacity to provide new targets for
the treatment of septic shock. In this regard, activation of the transcription
factor NF-kappaB is commonly thought to be critical to LPS-stimulated
macrophage inflammatory mediator production, although certain immunological,
genetic, and molecular evidence suggests that other factors are involved. To
address this issue, we hypothesized that the degree of LPS-induced NF-kappaB
mobilization should correlate with the murine endotoxicity of the species of
LPS used for in vitro study. Therefore, using D-galactosamine-sensitized mice,
we assessed the lethal potencies of eight LPS preparations from Escherichia,
Salmonella, Klebsiella, Bacteroides, Pseudomonas, Neisseria, and Rhodobacter
species as well as that of the endotoxin substructure lipid X. The lethal
potencies of these LPS preparations varied by > 160-fold. Treatment of RAW
264.7 cells with the same LPS preparations induced levels of tumor necrosis
factor alpha (TNF-alpha) and NO production that correlated with the LPS 50%
lethal dose. The combined analysis of the levels of these two mediators
produced in response to LPS in RAW cells was found to be a strong predictor of
murine endotoxic lethality. Interestingly, while relatively nontoxic in mice,
Rhodobacter capsulatus LPS stimulated RAW cell NF-kappaB-like DNA binding
protein mobilization and TNF-alpha production to levels comparable to those of
more toxic species of LPS but was unable to induce NO generation in RAW cells.
These data indicate that neither NF-kappaB activation nor TNF-alpha production
alone is a dependable predictor of LPS lethality. Additionally, cotreatment of
RAW cells with the potent inflammatory mediator ADP had no effect on the
ability of R. capsulatus LPS to stimulate NO production but significantly
enhanced induction of NO production by the toxic species of LPS. In contrast,
cotreatment of RAW cells or peritoneal macrophages with gamma interferon
(IFN-gamma) normalized the abilities of both toxic and nontoxic LPS
preparations to induce NO production, suggesting that selected preparations of
LPS may preferentially generate an IFN-gamma-like signal that accounts for
enhanced toxicity. In sum, the activation of NF-kappaB does not correspond to
LPS lethality, thereby complicating models of macrophage activation that
highlight NF-kappaB alone as a signal transduction factor necessary for
LPS-mediated toxicity.
PMID: 9529092, UI: 98187941


4. Transplantation 1997 Mar 15;63(5):636-9 
Effect of oral supplementation of ornithine-alpha-ketoglutarate on the
intestinal barrier after orthotopic small bowel transplantation.
de Oca J, Bettonica C, Cuadrado S, Vallet J, Martin E, Garcia A, Montanes T,
Jaurrieta E
Department of Surgery, University of Barcelona, Spain.

The aim of this study was to analyze the possible protective effects of a
glutamine and arginine precursor (ornithine-alpha-ketoglutarate [OKG]) on the
mucosa of a transplanted intestine when administered with either a defined
formula oral diet (DFD) or a standard chow. Isogenic male Lewis rats (250 g)
were submitted to a laparotomy (groups 1 and 2) or to an orthotopic small bowel
transplantation (SBT; groups 3-6). Groups 1, 3, and 5 received a DFD 14 days
after surgery. Groups 2, 4, and 6 received standard chow. In addition, groups
5 and 6 received a daily oral supplementation of 1.4 g/kg of OKG. Weight changes
and food intake were recorded daily. At the end of the study, bacterial
translocation (BT) was measured in mesenteric lymph nodes, liver, and spleen.
The protein/DNA index was also determined in intestinal mucosa. SBT induced BT
in all transplanted groups, especially in those fed DFD. Addition of OKG
(groups 5 and 6) significantly reduced BT in comparison with groups 3 and 4 and
improved the protein/DNA index as well as weight gain. It is concluded that OKG
supplementation protects the intestinal barrier after SBT, and that this effect
is more marked when it is added to a standard chow.
PMID: 9075830, UI: 97230252


5a. Surg Today 1997;27(5):447-9 
Bacterial translocation as a cause of septic shock in humans: a report of two
cases.
Tani T, Hanasawa K, Endo Y, Kurumi Y, Shiomi H, Kodama M, Kushima R, Hattori T
First Department of Surgery, Shiga University of Medical Science, Japan.

While bacterial translocation has been reported to occur under numerous
conditions in animal models, there has been no paper to date focusing on
bacterial translocation as a direct cause of septic shock in humans. We present
herein the cases of two patients who developed septic shock believed to have
been directly caused by bacterial translocation. Neither of the patients had a
focus of infection, the intestinal walls were intact in gross appearance, and
the peritoneal cavity had not been contaminated by surgery. Moreover, in both
patients, the same organisms were detected in the blood, ascites fluid, and
mesenteric lymph nodes, and bacilli were found in the intestinal wall.
PMID: 9130349, UI: 97276596

5b. J Pediatr Surg 1994 Feb;29(2):280-5; discussion 285-7 
Bacterial translocation in mesenteric ischemia-reperfusion injury: is
dysfunctional motility the link?
Hebra A, Hong J, McGowan KL, Smith C, McKernan ML, Ross AJ 3rd
David Paley Lichtenstein Laboratory of Surgical Metabolism and Nutrition,
Children's Hospital of Philadelphia, PA 19104.

The authors previously reported that mesenteric ischemia and reperfusion (I/R)
in a chronic newborn piglet model creates dysfunctional intestinal motility.
Whether this leads to inadequate bacterial clearance and translocation (BT)
through the gastrointestinal tract remains unclear. To test this hypothesis the
authors used their chronic piglet model (weight, 3.5 +/- 0.3 kg; age, 18 +/- 4
days; on formula feeding); nonocclusive mesenteric ischemia was induced via
reversible pericardial tamponade. Mesenteric flow (SMA Doppler measurement via
the retroperitoneal approach) was decreased to 25% +/- 5% of baseline for 300
minutes in the ischemia group (n = 7) and followed by 14 hours of reperfusion
in the I/R group (n = 6). Control subjects had a sham operation (n = 7).
Mesenteric lymph nodes (MLN), liver (L), spleen (S), ileum, peritoneum, and
blood were harvested for blind quantitative microbial analysis. Subjects in the
control group had no cultures positive for growth. Eighty-five percent of
animals in the ischemia group had positive MLN cultures only (P < .05 v
control). All piglets in the I/R group had positive MLN cultures (P < .05 v
control), and one third of them manifested bacteremia. Histological examination
did not show mucosal disruption in any group. The validity of this model is
confirmed by the negative cultures in the control group and by the presence of
normal ileal flora in all animals. In the ischemia and I/R groups, MLN cultures
were consistently positive with gram-negative bacilli (Escherichia coli and/or
Klebsiella pneumoniae). When subjects of the I/R group had more than 1,000
colonies in the MLN, bacteremia with the translocating organisms was also
identified.
PMID: 8176606, UI: 94231423

5c. Br J Surg 1993 Jul;80(7):901-2 
Translocation of enteric bacteria in humans.
Brooks SG, May J, Sedman P, Tring I, Johnstone D, Mitchell CJ, MacFie J
Department of General Surgery, Scarborough Hospital, UK.
Comments:  Comment in: Br J Surg 1994 Mar;81(3):470-1
PMID: 8369931, UI: 93379836

5d. J Infect Dis 1991 Nov;164(5):917-21 
Oral aminoglycoside and ofloxacin therapy in the prevention of gram-negative
sepsis after irradiation.
Brook I, Ledney GD
Experimental Hematology Department, Armed Forces Radiobiology Research
Institute, Bethesda, Maryland 20889-5145.

To investigate whether oral gentamicin or ofloxacin therapy protects against
gram-negative sepsis after irradiation, B6D2F1 mice were exposed to 7.5 Gy of
radiation from 60Co, infected with 10(7) Pseudomonas aeruginosa or Klebsiella
pneumoniae orally 3 days after irradiation, and treated with oral (15
mg/kg/day) or intramuscular (im; 7.5 mg/kg/day) gentamicin or oral (40
mg/kg/day) ofloxacin. For P. aeruginosa, gentamicin therapy was started orally
10 and 24 h and im 24 h after inoculation. For K. pneumoniae, gentamicin was
started orally 24, 48, and 72 h and im 24 h after inoculation; ofloxacin was
started 24 h after inoculation. Mice that received oral gentamicin early (10 h
for P. aeruginosa, 24 h for K. pneumoniae), im gentamicin, or oral ofloxacin
showed significantly (P less than .05) reduced colonization, translocation, and
mortality compared with mice that received oral gentamicin late. These data
support the use of selective antimicrobial therapy to reduce colonization,
translocation, and mortality from gram-negative bacteria in irradiated animals.
PMID: 1940469, UI: 92043903


6. Hepatology 1996 Apr;23(4):781-7 
Selective intestinal decontamination with norfloxacin reduces bacterial
translocation in ascitic cirrhotic rats exposed to hemorrhagic shock.
Llovet JM, Bartoli R, Planas R, Vinado B, Perez J, Cabre E, Arnal J, Ojanguren
I, Ausina V, Gassull MA
Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol,
Badalona, Catalunya, Spain.

Bacterial translocation (BT) can be involved in the pathogenesis of severe
infections due to bacteria of enteric origin that complicates bleeding
cirrhotic patients. To assess the effect of hemorrhagic shock (HS) on the
incidence of BT and if selective intestinal decontamination (SID) reduces this
incidence, we studied six groups of Sprague-Dawley rats: ascitic rats, ascitic
rats exposed to HS with and without previous norfloxacin prophylaxis, healthy
rats, and healthy shocked rats with and without previous norfloxacin
prophylaxis. BT tended to be higher in ascitic rats with shock than without
shock (69% vs. 41%, P = .15) and was significantly higher in healthy rats with
than without shock (50 percent vs. 0 percent, P = .01). Norfloxacin
significantly reduced translocation in ascitic shocked rats in comparison with
nondecontaminated ascitic shocked rats (31 percent vs. 69 percent, P = .038).
This effect was due mainly to a reduction of gram-negative BT (O percent vs. 37
percent, P = .008). In addition, norfloxacin prevented translocation in healthy
shocked rats. Accordingly, aerobic gram-negative bacteria disappeared from
fecal flora in all rats administered norfloxacin, except for Klebsiella species
in one control rat. Cecal severe submucosal edema, chronic inflammatory
infiltrate, and intestinal lymphangiectasia were significantly more frequent in
ascitic rats than in control rats. Intestinal mucosal injury related with HS,
particularly subepithelial cecal edema, was observed only in ascitic shocked
rats. In conclusion, HS increases the incidence of BT both in ascitic cirrhotic
and healthy rats. Norfloxacin reduces significantly the incidence of
translocation after shock, especially in those cases caused by aerobic
gram-negative bacilli.
PMID: 8666332, UI: 96230102


7. Arch Surg 1996 Feb;131(2):176-9 
Microbial translocation in neonates and infants receiving long-term parenteral
nutrition.
Pierro A, van Saene HK, Donnell SC, Hughes J, Ewan C, Nunn AJ, Lloyd DA
Department of Paediatric Surgery, Institute of Child Health, London, England.

OBJECTIVE: To explore whether episodes of endogenous septicemias due to
microbial translocation are clinically relevant in neonates and infants who are
receiving long-term parenteral nutrition (PN). DESIGN: Prospective
observational cohort study of 2 years. SETTING: Neonates and infants who
underwent surgical procedures and required PN because of gastrointestinal
abnormalities. MEASUREMENTS: Surveillance cultures of the oropharynx and gut
were obtained at the first of PN and thereafter twice each week. These cultures
were processed for all microorganisms, except for coagulase-negative
staphylococci, in a semiquantitative manner to detect overgrowth. A blood
sample was taken for culture from both the central venous line and peripheral
vein on clinical indication only. Microbial translocation was diagnosed when
the microorganisms that were isolated from the blood sample were also carried
in the throat and/or rectum within the 2 weeks preceding the episode of
septicemia. MAIN RESULTS: Of 94 infants, 10 (11%) experienced 24 episodes of
septicemia (ie, 7.3 septicemic episodes per 1000 days of PN). Six infants
experienced 15 episodes of microbial translocation due to enteric
microorganisms, including Escherichia coli, Klebsiella, Candida species, and
enterococci. Microbial translocation occurred after a median of 58 days of PN
(range, 32 to 286 days). The enteric organisms that caused septicemia were
always present in the throat and/or rectum and in high concentrations ( > 10(5)
colony-forming units per gram [ie, overgrowth]) in 60% of the translocation
episodes. All but one episode occurred in infants with an abnormal serum
bilirubin level ( > 17 mumol/L [0.99 mg/dl]). CONCLUSIONS: In neonates and
infants who are receiving PN, septicemia may be a gut-related phenomenon.
PMID: 8611075, UI: 96190360

8. Kansenshogaku Zasshi 1995 Sep;69(9):1017-20 
[A case of gas-containing liver abscess with multiple metastatic lesions].
[Article in Japanese]
Higashi T, Makino Y, Katsurada K
Department of Emergency Medicine, Osaka Prefectural General Hospital.

A 63-year-old male was admitted to our hospital because of high fever and
delirium. He had been diagnosed as diabetes mellitus five years before but not
treated at all. An abdominal CT scan showed gas-containing abscess in the right
lobe of the liver. Klebsiella pneumoniae and Bacteroides distasonis were
cultured both from the punctured specimen of the abscess and from arterial
blood. Catheter drainage was carried out percutaneously under guidance with
ultrasonography and antibiotics was administered intravenously. He was
diagnosed as purulent meningitis by lumbar puncture on admission and as
endophthalmitis because of swelling of the left eyeball on hospital day 4. CT
scan also showed multiple metastatic lesions in the cerebrum and in the lung.
After three months, he was discharged from the hospital in good condition,
except for loss of vision of the left eye.
PMID: 7594794, UI: 96056832

9. Dig Dis Sci 1994 Jan;39(1):157-60 
Translocation of bacteria due to direct mucosal damage caused by Gastrografin.
An experimental study in newborn rats.
Feigenberg Z, Levavi H, Ben-Baruch D, Abramovici A
Department of Surgery A, Beilinson Medical Center, Petah Tikva, Israel.

A study was carried out on 40 newborn rats to determine the effect of
Gastrografin (a hyperosmolar solution, 1700 mosm/liter) on the gastrointestinal
tract. All the newborns received an inoculum of Klebsiella bacteria to the
gastrointestinal tract. Thirty received, in addition to maternal milk, a
feeding of Gastrografin twice daily. The Gastrografin was found to cause severe
and irreversible damage to the mucosa of the small intestine, causing the death
of 24 rats less than a week after start of the experiment. The 10 rats who
received no Gastrografin and served as controls showed no signs of disease or
damage to the intestinal tract. Cultures taken from the peritoneal cavity after
sacrifice were all positive for Klebsiella in the Gastrografin group (30 rats)
and negative in the controls (10 rats). This study has therefore demonstrated
that severe damage to the small intestine mucosa will lower the intestinal
barrier and lead to transmural translocation of bacteria into the peritoneal
cavity.
PMID: 8281851, UI: 94109245


10. Mol Microbiol 1993 Aug;9(4):857-68 
Characterization of pilQ, a new gene required for the biogenesis of type 4
fimbriae in Pseudomonas aeruginosa.
Martin PR, Hobbs M, Free PD, Jeske Y, Mattick JS
Centre for Molecular Biology and Biotechnology, University of Queensland,
Brisbane, Australia.

Type 4 fimbriae are produced by a variety of pathogens, in which they appear to
function in adhesion to epithelial cells, and in a form of surface
translocation called twitching motility. Using transposon mutagenesis of
Pseudomonas aeruginosa, we have identified a new locus required for fimbrial
assembly. This locus contains the gene pilQ which encodes a 77 kDa protein with
an N-terminal hydrophobic signal sequence characteristic of secretory proteins.
pilQ mutants lack the spreading colony morphology characteristic of twitching
motility, are devoid of fimbriae, and are resistant to the fimbrial-specific
bacteriophage PO4. The pilQ gene was mapped to Spel fragment 2, which is
located at 0-5 minutes on the P. aeruginosa PAO1 chromosome, and thus it is not
closely linked to the previously characterized pilA-D, pilS,R or pilT genes.
The pilQ region also contains ponA, aroK and aroB-like genes in an organization
very similar to that of corresponding genes in Escherichia coli and Haemophilus
influenzae. The predicted amino acid sequence of PilQ shows homology to the
PulD protein of Klebsiella oxytoca and related outer membrane proteins which
have been found in association with diverse functions in other species
including protein secretion, DNA uptake and assembly of filamentous phage. PilQ
had the highest overall homology to an outer membrane antigen from Neisseria
gonorrhoeae, encoded by omc, that may fulfil the same role in type 4 fimbrial
assembly in this species.
PMID: 7901733, UI: 94049125

11. Antimicrob Agents Chemother 1991 Aug;35(8):1576-81 
Translocation of antibiotic resistance determinants including an
extended-spectrum beta-lactamase between conjugative plasmids of Klebsiella
pneumoniae and Escherichia coli.
Sirot D, De Champs C, Chanal C, Labia R, Darfeuille-Michaud A, Perroux R, Sirot
J
Laboratoire de Bacteriologie, Faculte de Medecine, Clermont-Ferrand, France.

The extended-spectrum beta-lactamase CAZ-7, derived from TEMs, was produced by
two different strains of the family Enterobacteriaceae, Klebsiella pneumoniae
and Escherichia coli, isolated from the same patient. Both isolates were
resistant to amikacin. In addition, the K. pneumoniae strain was TEM-1
producing and resistant to gentamicin. An E. coli HB101 transconjugant obtained
from K. pneumoniae, selected on ceftazidime, showed that CAZ-7 and amikacin
resistance were encoded by an 85-kb Inc7 or M plasmid, while an E. coli HB101
transconjugant obtained from E. coli under the same conditions showed that
CAZ-7 and amikacin resistance were encoded by a greater than 150-kb Inc6 or C
plasmid. Two other E. coli HB101 transconjugants obtained from K. pneumoniae,
selected on gentamicin or chloramphenicol, showed that TEM-1 and gentamicin
resistance could be encoded either by a greater than 150-kb Inc6 or C plasmid
or by an 85-kb Inc7 or M plasmid. It was hypothesized that the genes for
beta-lactam and aminoglycoside resistances were located on translocatable
sequences. EcoRI digestion and hybridizations obtained with blatem, aacA4, and
IS15 probes demonstrated that the CAZ-7 gene, amikacin resistance gene, and
IS15 element were clustered on an approximately 20-kb fragment common to 85-
and greater than 150-kb plasmids. E. coli HB101 transconjugants from K.
pneumoniae and E. coli isolates were used to obtain translocations of CAZ-7 and
amikacin resistance and of TEM-1 and gentamicin resistance between the 85- and
greater than 150-kb plasmids. This study shows a typical example of in vivo
gene dissemination involving transposable elements which translocate
multiresistance genes, including an extended-spectrum beta-lactamase.
PMID: 1929328, UI: 92027656

12. Infect Immun 1989 Aug;57(8):2495-501 
Trehalose dimycolate enhances resistance to infection in neutropenic animals.
Madonna GS, Ledney GD, Elliott TB, Brook I, Ulrich JT, Myers KR, Patchen ML,
Walker RI
Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20814-5145.

Bacterial infections are lethal complications of neutropenia, and antibiotics
alone are inadequate therapy for these infections. Irradiated mice become
severely neutropenic and remain susceptible to infection for 2 to 3 weeks,
depending on the dose and quality of radiation. Some bacterial cell wall
derivatives stimulate nonspecific host defense mechanisms against a variety of
microbes which might cause postirradiation infection. In this study we
determined if the cell wall glycolipid trehalose dimycolate (TDM), derived from
Mycobacterium phlei, or a synthetic preparation of TDM was able to (i) enhance
survival in mice when given before or after lethal doses of 60Co radiation and
(ii) increase nonspecific resistance to postirradiation infection. Treatment
with TDM oil-in-water emulsions and with synthetic TDM significantly enhanced
survival before and after lethal doses of 60Co irradiation. This result
correlated with the ability of TDM to reduce the translocation of intestinal
bacteria and to stimulate hematopoiesis. With respect to nonspecific resistance
to infection, TDM injected 1 h after sublethal irradiation increased resistance
to a lethal Klebsiella pneumoniae challenge (10 50% lethal doses of K.
pneumoniae in 30 days [LD50/30]) 4 or 14 days later. Increasing the dose of K.
pneumoniae to 5,000 LD50/30 on day 4 overwhelmed the ability of TDM-treated
mice to overcome infection. However, TDM treatment 1 h postirradiation combined
with ceftriaxone antibiotic therapy (days 5 through 14) enhanced survival, even
when the higher dose of bacteria (5,000 LD50/30) was used. These results
indicate that in irradiated mice, TDM can be used to enhance survival and, as
a potent stimulant of nonspecific resistance to infection in neutropenic mice,
can act synergistically with antibiotic therapy to reduce sepsis and mortality.
PMID: 2663726, UI: 89307570

13. Acta Microbiol Hung 1988;35(1):49-54 
Bacterial translocation in dianhydrodulcitol-treated mice.
Anderlik P, Szeri I, Banos Z
Institute of Microbiology, Semmelweis University Medical School, Budapest,
Hungary.

Escherichia, Proteus, Klebsiella and Streptococcus strains were isolated from
mesenteric lymph nodes, spleens and livers of conventional mice treated with
dianhydrodulcitol (DAD), indicating that intestinal bacteria had appeared in
organs usually containing no bacteria. The frequency of bacterial translocation
showed direct relation to the dose of the drug and appeared simultaneously with
the spleen atrophy caused by DAD.
PMID: 3293340, UI: 88278962

14. Can J Microbiol 1984 Nov;30(11):1344-8 
Endogenous infection in mice with streptozotocin-induced diabetes. A feature of
bacterial translocation.
Imai A, Kurihara Y

Slc:ddY mice that received a single intraperitoneal injection of 200 mg/kg
streptozotocin (STZ) were examined for persistency of diabetes (changes of
indigenous bacterial floras, and bacterial translocation. Significant diabetes
(increase in plasma glucose and decrease in insulin) was recognized 2 weeks
after the injection, and persisted for 12 weeks. The numbers of aerobic
gram-negative bacilli, staphylococci (including micrococci), and streptococci
in caecal and oral floras were significantly increased, but the numbers of
anaerobic bacteria in caecal flora were hardly changed. Bacterial translocation
of indigenous bacteria to the mesenteric lymph node, lung, or kidney was
detectable in some mice 2 weeks after the injection. The incidence of bacterial
translocation in these STZ-treated mice then increased; infection caused by
several organisms, e.g., Klebsiella pneumoniae, Staphylococcus epidermidis,
streptococci, or Lactobacillus sp., occurred in lung, liver, spleen, kidneys,
and mesenteric lymph node. No indigenous bacteria were cultured from these
organs of control mice. This endogenous infection may have been due to the over
population of several bacterial strains caused by disruption of indigenous
floras along with depression of immunological function.
PMID: 6240312, UI: 85098883

15. Infect Immun 1983 Mar;39(3):1252-9 
Relationship between cecal population levels of indigenous bacteria and
translocation to the mesenteric lymph nodes.
Steffen EK, Berg RD

Translocation is defined as the passage of viable bacteria from the
gastrointestinal tract to the mesenteric lymph nodes (MLN) and other organs.
The extent of translocation of certain indigenous, oxygen-tolerant bacteria
from the cecum to the MLN, spleen, liver, kidney, and peritoneal cavity were
determined in diassociated or triassociated gnotobiotic mice. Minimal bacterial
translocation occurred to the spleen, liver, kidney, or peritoneal cavity.
However, most bacterial strains readily translocated to the MLN. The percentage
of the total population of each bacterial strain in the ceca was compared with
the percentage of the total population of that strain in the MLN. There was a
direct relationship between the numbers of a particular bacterial strain
populating the ceca of diassociated or triassociated mice and the numbers of
viable bacteria of this strain present in the MLN. Thus, the cecal population
level of a particular bacterial strain determined the numbers of viable
bacteria of this strain translocating to the MLN. The translocation of these
bacterial strains from the gastrointestinal tract is an important first step in
the pathogenesis of infection caused by members of the normal intestinal
microflora.
PMID: 6341234, UI: 83184660

16a. Infect Immun 1997 Apr;65(4):1546-9 
Binding of the type 3 fimbriae of Klebsiella pneumoniae to human endothelial
and urinary bladder cells.
Tarkkanen AM, Virkola R, Clegg S, Korhonen TK
Department of Biosciences, FIN-00014 University of Helsinki, Finland.

Binding of the two identified type 3 fimbrial variants of Klebsiella pneumoniae
to human endothelial EA-hy926 and bladder T24 cells was assessed. The
recombinant Escherichia coli strain LE392(pFK12), expressing plasmid-encoded
type 3 fimbriae of K. pneumoniae, adhered to both cell lines, and the fimbriae
purified from the strain bound to both cell lines in a dose-dependent manner.
Adhesiveness to both cell lines of chromosomally encoded type 3 fimbriae from
K. pneumoniae IApc35 was lower. No binding was detected with type 1 fimbriae of
K. pneumoniae. Both type 3 fimbrial variants exhibited a significantly lower
affinity for the cell lines than did S fimbriae of meningitis-associated E.
coli.
PMID: 9119502, UI: 97230338

16b. Infect Immun 1995 Oct;63(10):4046-53 
Activation of human endothelial cells by viable or heat-killed gram-negative
bacteria requires soluble CD14.
Noel RF Jr, Sato TT, Mendez C, Johnson MC, Pohlman TH
Department of Surgery, University of Washington School of Medicine, Seattle
98104, USA.

In response to bacterial lipopolysaccharides (LPS; endotoxin), endothelial
cells are converted to an activation phenotype expressing both proinflammatory
and procoagulant properties that include the induction of leukocyte adhesion
molecules and tissue factor expression. LPS-induced endothelial cell activation
requires a soluble form of the monocyte LPS receptor, sCD14. We evaluated the
capacity of multiple strains of gram-negative and gram-positive bacteria to
induce endothelial E-selectin and tissue factor expression through
sCD14-dependent pathways with cultured human umbilical vein endothelial cells
(HUVE). Both viable and heat-killed gram-negative bacteria (Bacteroides
fragilis, Enterobacter cloacae, Haemophilus influenzae, and Klebsiella
pneumoniae) but not viable or heat-killed gram-positive bacteria
(Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae)
induced prominent E-selectin surface expression detected by enzyme-linked
immunosorbent assay. Tissue factor activity on HUVE, indicated by factor X
activation, was induced in response to gram-negative bacteria but not in
response to gram-positive bacteria. Gram-negative bacteria induced
transcriptional activation in HUVE, indicated by the appearance of
E-selectin-specific mRNA and by the demonstration of activation of NF-kappa B,
a trans-activating factor necessary for E-selectin and tissue factor gene
transcription. In contrast, neither E-selectin mRNA nor activation of NF-kappa
B was detected in HUVE treated with gram-positive bacteria. Endothelial cell
activation by gram-negative bacteria in each of these assays was inhibited with
a monoclonal antibody (60bd) against CD14. Furthermore, CHO-K1 cells,
transfected with human recombinant CD14, responded to all strains of
gram-negative bacteria (viable or heat killed), indicated by CHO-K1 NF-kappa B
activation. We conclude that gram-negative bacteria induce endothelial cell
activation through a common sCD14-dependent pathway.
PMID: 7558318, UI: 96009765

17. A preliminary analysis of bbb infections and sequalae therefrom
HTTP://www.jorsm.com/~binstock/bbb-inf.htm