Dorota Wojnicz, Dorota Tichaczek-Goska, Agnieszka Cisowska
Effect of Subinhibitory Concentrations
of Amikacin and Ciprofloxacin on the K1 Antigen
Expression and Phagocytosis of
Escherichia coli
Strains
Wpływ stężeń subinhibicyjnych amikacyny i ciprofloksacyny
na ekspresję antygenu K1 oraz fagocytozę szczepów Escherichia coli
Department of Biology and Medical Parasitology, Wroclaw Medical UniversityAbstract
Background. Escherichia coli strains with capsular Kl antigen are the major cause of neonatal meningitis and are also responsible for a large number of cases of bacteraemia and urinary tract infections in children and adults. The polysaccharide K1 antigen of E. coli is an important virulence factor that increases resistance to phagocytosis. Although the subinhibitory concentrations (sub-MICs) of antibiotics do not kill microorganisms, they are able to modulate their characteristics,e.g., the morphology of cells, the bacterial surface components. As a result a reduc-tion of bacterial pathogenicity is observed. This may also be associated with changes in the susceptibility of patho-gens to the host immune response.
Objectives. The aim of this study was to evaluate the influence of sub-MICs of amikacin and ciprofloxacin on the presence of cell-surface K1 antigen of uropathogenic E. coli strains and their phagocytosis by neutrophils.
Material and Methods. Fifteen E. coli strains expressing K1 antigen were selected from among the one hundred and twenty samples isolated from the urine of children with urinary tract infections. The bacteriophage K1A was used to detect the presence of the capsular antigen K1. The MICs of amikacin and ciprofloxacin for each strain incubated in Mueller-Hinton broth were obtained by microdilution method. The phagocytic index was determined by microscopic examination of slides prepared with May-Grünwald stain.
Results. Exposure of E. coli K1 strains to 1/2, 1/4 and 1/8 of MICs of amikacin and ciprofloxacin reduced the number of clones sensitive to K1A phage, however the effect of amikacin was minute. Moreover, changes in the susceptibility to phagocytosis of E. coli strains incubated in the presence of antibiotics were observed.
Conclusions. The treatment of encapsulated bacteria with sub-MICs of amikacin or ciprofloxacin inhibits the K1 capsule expression and enhances phagocytosis by human neutrophils (Adv Clin Exp Med 2010, 19, 4, 429–436).
Key words: Escherichia coli, K1 antigen, phagocytosis, subinhibitory concentrations, antibiotics.
Streszczenie
Wprowadzenie. Szczepy Escherichia coli z otoczkowym antygenem K1 są częstą przyczyną zapalenia opon mózgo-wo-rdzeniowych u noworodków, przypadków bakteriemii oraz zakażeń układu moczowego u dzieci i dorosłych. Polisacharydowy antygen K1 pałeczek E. coli jest ważnym czynnikiem wirulencji, który zwiększa oporność na fagocytozę. Mimo, że stężenia subinhibicyjne antybiotyków (sub-MICs) nie zabijają bakterii, mogą zmieniać ich cechy fenotypowe, np. morfologię komórek, czy struktury powierzchniowe. W wyniku tego obniża się patogenność mikroorganizmów oraz zmienia się ich podatność na odpowiedź immunologiczną gospodarza.
Cel pracy. Określenie wpływu sub-MICs amikacyny i ciprofloksacyny na zdolność syntezy powierzchniowego antygenu K1 przez uropatogenne pałeczki E. coli oraz ich fagocytozę przez neutrofile.
Materiał i metody. W badaniach wykorzystano piętnaście szczepów E. coli K1 spośródstu dwudziestu izolatów otrzymanych z moczu dzieci z zakażeniem dróg moczowych. Obecność antygenu K1 na powierzchni komórek bakterii oznaczono za pomocą faga K1A. Wartości MIC amikacyny i ciprofloksacyny wobec badanych pałeczek oznaczono metodą mikrorozcieńczeń w podłożu Mueller-Hinton. Na podstawie mikroskopowej oceny rozmazów krwi barwionych odczynnikiem May-Grünwalda określono indeks fagocytarny.
Wyniki. Liczba klonów szczepów E. coli K1 wrażliwych na faga K1A poddanych działaniu 1/2, 1/4 oraz 1/8 MIC amikacyny lub ciprofloksacyny zmniejszyła się, w przypadku amikacyny obserwowane zmiany nie były jednak
Adv Clin Exp Med 2010, 19, 4, 429–436 ISSN 1230-025X
OrIGINAL PAPErS
Escherichia coli strains with capsular Kl anti-gen are the major cause of neonatal meningitis and arealso responsible for a large number of cases of bacteraemia and urinary tract infections in chil-dren and adults [1]. The cell surface antigen K1, such as the capsule of group B meningococci, is a linear homopolymer of α-2-8-linked N-acetyl-neuraminic acid (NeuNAc) and is poorly immu-nogenic, because NeuNAc residues are also found in gangliosides and many mammalian serum and cell membrane glycoproteins [2]. K antigens of
E. coli have been described as virulence factors be-cause of their higher incidence in strains causing invasive infections. The greater virulence of bac-terial cells possessing polysaccharide capsules may be explained by interference of the K antigen with polymorphonuclear leukocytes responsible for phagocytosis. The capsule may provide protection to the microorganism by maskingits underlying opsonized surface and serving as a physical barrier to the phagocytic cells [3].
It is well known that subinhibitory concentra-tions (sub-MICs) of antibiotics are able to modu-late numerous bacterial characteristics, e.g., the morphology of cells, the bacterial surface compo-nentssuch as outer membrane proteins and lipo-polysaccharides,and other virulence factors [4–6]. The aim of this investigation was to evaluate the influence of sub-MICs of amikacin and cipro-floxacin on the presence of cell-surface K1 antigen of uropathogenic E. coli strains and their phagocy-tosis by neutrophils. In addition to these studies, the authors determined the relationship between the percentage of clones of E. coli possessing anti-gen K1 and the value of phagocytic indexes.
Material and Methods
Bacterial Strains
E. coli isolates (n = 120) were isolated from the urine of children with different clinical variants of urinary tract infection, hospitalised in Korczak Paediatric Centre of Lower Silesia in Wroclaw.
Antibiotics
Amikacin (Biodacyna, Warsaw, Poland) and ciprofloxacin (Proxacin, Warsaw, Poland) were used.
Antimicrobial Susceptibility
Testing
MIC assay of two antimicrobial agents for
E. coli K1 strains were performed in Mueller-Hin-ton broth according to CLSI guidelines for broth microdilution susceptibility testing [7].
Detection of Capsular
Antigen K1
The K1-specific bacteriophage (K1A) was used for detection of this antigen according to the pro-cedure described by Devine et al. [8]. The E. coli
strains were grown overnight in the absence or presence of sub-MICs of amikacin or ciprofloxa-cin (1/2, 1/4, 1/8 of MIC). The bacterial cells were then inoculated into 4 ml of nutrient broth and in-cubated at 37°C for 4 h. Next a single streak of each culture was made on nutrient agar and allowed to dry. Once the streak was dry, 10 µl of bacterio-phage suspension was placed in the centre. After incubation at 37°C for 18 h, the presence of K1 was indicated by a reduction in the density of bacterial growth where the bacteriophage suspension had been placed. Phage K1A and the standard strain
E. coli B2095 (O2:K1) used for proliferation of the phage were from the collection of Dr. G. Schmidt (Forschungsinstitut Borstel, Institut für Experi-mentelle Biologie und Medizin, Germany).
Phagocytic Activity of
Neutrophil Granulocytes
and Phagocytic Index
The neutrophil phagocytic activity was observed in the in vitro experiment using whole blood taken from 4 healthy adult volunteers. The E. coli strains were grown overnight in the absence or presence of sub-MICs of amikacin or ciprofloxacin (1/2, 1/4, 1/8 of MIC). Bacteria were harvested, washed and standardized spectrophotometrically to obtain suspensions containing 5 × 108 cfu/ml. Then 200
μl of blood was incubated for 1 h at 37°C with 200 μl of heat-killed E. coli cell suspension. Immedi-ately after incubation, two May-Grünwald stained smears of blood were prepared from each sample according to the conventional methodology. The
znaczące. Ponadto zaobserwowano zwiększoną podatność na fagocytozę bakterii inkubowanych w obecności anty-biotyków.
Wnioski. Działanie sub-MICs amikacyny i ciprofloksacyny hamuje zdolność syntezy antygenu K1 przez pałeczki
E. coli oraz zwiększa ich fagocytozę (Adv Clin Exp Med 2010, 19, 4, 429–436).
phagocytic index was calculated as the average number of bacterial cells ingested by one phago-cytic cell out of fifty randomly selected neutrophils examined. Experiments were performed in dupli-cate on three separated occasions.
Statistical Analysis
All experiments were performed indepen-dently in duplicate on three separate occasions. Values were expressed as mean ± SD. The effects of antibiotics at various sub-MICs were quantita-tively evaluated by one-way analysis of variance (ANOVA). The expression of K1 antigen and the values of phagocytic index were compared before and after exposure of E. coli strains to antibiotics using Student’s pair t-test. P values ≤ 0.05 were considered to be statistically significant.
Results
In the preliminary studies, the authors deter-mined the ability of uropathogenic E. coli strains to produce K1 antigen. Fifteen of the 120 E. coli
iso-lates synthesized this polysaccharide capsule. Then we evaluated the MICs of antibiotics suppressing the growth of E. coli strains expressing K1 anti-gen. For individual strains the MICs of amikacin and ciprofloxacin varied in the range 0.5 µg/ml – 4.0 µg/ml and 0.007 µg/ml – 32 µg/ml, respectively (Table 1).
The effect of antibiotics on the loss or changes of the capsular K1 antigen by E. coli strains was es-timated by examining the sensitivity to K1A phage of fifteen E. coli K1 strains exposed to sub-MICs of amikacin or ciprofloxacin. The same set of strains not exposed to antibiotics was used as a control. The authors tested one hundred clones of each
E. coli K1 strain, either antibiotic-treated bacteria or not (Table 2). In controls (without antibiotics), all tested E. coli K1 strains revealed the occurrence of 97–98% clones with K1 antigen. The exposure of
E. coli K1 strains to sub-MICs of ciprofloxacin de-creased the percentage of clones with K1 antigen. The number of clones of E. coli K1 strains sensi-tive to K1A phage exposed to 1/2, 1/4 and 1/8 of MICs of ciprofloxacin was suppressed to 73– 76%, 77–81% and 80–82%, respectively. For all studied
E. coli strains a statistically significant difference was seen between the controls and bacteria treated with the sub-MICs of ciprofloxacin (p < 0.05). The authors observed also that after incubation of E. coli
K1 strains in 1/2, 1/4 and 1/8 of MICs of amikacin, the percentage of clones with K1 antigen was slightly lower (90–93%) compared with the control sample. Expression of K1 capsule was not significantly dif-ferent between rods treated with sub-MICs of ami-kacin in comparison with the untreated bacteria, for all studied strains (p > 0.05).
In the next stage the effect of sub-MICs of both antibiotics in the susceptibility of E. coli K1 strains to phagocytosis by neutrophils was determined. In preparations of the blood smear bacterial cells in-gested by fifty neutrophils were counted and then the phagocytic index for each tested strain was calculated (Table 3 and 4). These values for the control samples (incubation without antibiotics) were 10.2 ± 1.6–12.2 ± 1.8 (Fig. 1). The incubation of rods in the presence of ciprofloxacin increased their susceptibility to phagocytosis, and the aver-age number of bacterial cells, which were absorbed by phagocytes was 13.4 ± 1.4–19.2 ± 1.5. The high-est values of the phagocytic index, from 17.2 ± 1.5 to 19.2 ± 1.5, were observed for all studied
E. coli strains incubated at ciprofloxacin concen-tration equal to 1/2 of MIC (Fig. 1) and this result was found to be statistically significant (p < 0.05). Bacteria exposed to 1/4 and 1/8 of MIC of cipro-floxacin had a lower sensitivity to phagocytosis. The phagocytic indexes ranged from 14.2 ± 1.7 to 15.8 ± 1.5 and from 13.4 ± 1.4 to14.8 ± 1.4,
respec-Table 1. MIC values of amikacin and ciprofloxacin against E. coli strains
Tabela 1. Wartości MIC amikacyny i ciprofloksacyny dla badanych szczepów E. coli
E. coli strains
(Szczepy
E. coli)
MIC (µg/ml) Amikacin
(Amikacyna) Ciprofloxacin (Ciprofloksacyna)
1 2.0 0.031
2 0.5 0.007
3 0.5 0.007
4 0.5 0.015
5 4.0 32.0
6 1.0 0.007
7 1.0 0.031
8 0.5 0.007
9 1.0 0.031
10 0.5 0.007
11 4.0 8.0
12 1.0 0.031
13 0.5 0.007
14 0.5 0.015
tively. The phagocytic indexes were significantly different only between bacteria treated with 1/4 of MIC of ciprofloxacin and the control samples, for all studied E. coli strains (p < 0.05).
Moreover, changes in susceptibility to phago-cytosis of E. coli strains incubated in the presence of amikacin have been observed. The exposure of rods to 1/2 of MIC of amikacin caused enhanced ingestion of bacteria by neutrophils in comparison with control samples, this effect was statistically sig-nificant for all studied E. coli strains (p < 0.05). The values of phagocytic index ranged from 14.2 ± 1.8 to 16.2 ± 1.5. The lower phagocytic indexes occurred after treatment of bacteria with 1/4 and 1/8 of MIC of amikacin. The average number of bacterial cells ingested by neutrophils were 13.2 ± 1.4 – 14.9 ± 1.7 and 12.8 ± 1.8 – 13.8±1.6, respectively. These changes were not statistically significant for the most studied E. colistrains (p > 0.05).
Own results show a relationship between the average percentage of clones possessing K1 antigen and number of ingested bacteria by neutrophils
observed in the case of E. coli strains unexposed as well as exposed to sub-MIC of antibiotics (Fig. 2). Ciprofloxacin appeared to be more effective than amikacin in inducing changes in both respects, which depended on the antimicrobial agents con-centrations. The phagocytic index values were higher for thosestrains which possessed less K1A phage-sensitive clones, however the observed dif-ferences were not significant for all studied strains (p > 0.05).
Discussion
The presence of capsular polysaccharide anti-gens is an important virulence factor of gram-neg-ative and gram-positive bacteria [9, 10]. E. coli is no exception to this phenomenon. The presence of the K1 serotype capsular antigen results in reduced phagocytosis, decreased susceptibility to bacteri-cidal action of serum and has been associated with not only neonatal meningitis but also bacteraemia
Table 2. The sensitivity of E. coli K1 strains, unexposed and exposed to sub-MICs of amikacin and ciprofloxacin, to phage K1Aa
Tabela 2. Wrażliwość szczepów E. coli K1 niepoddanych i poddanych działaniu stężeń subinhibicyjnych amikacyny i ciprofloksacyny na faga K1Aa
E. coli strains
(Szczepy E. coli) Clones sensitive to phage K1A [%](Klony wrażliwe na faga K1A [%])
without antibiotic sub-MICs of amikacin sub-MICs of ciprofloxacin
1/2 1/4 1/8 1/2 1/4 1/8
1 97 91 93 93 76 80 81
2 97 91 93 93 73 80 82
3 98 91 93 93 75 81 82
4 98 90 91 93 73 80 82
5 98 91 92 92 75 78 81
6 98 91 92 92 75 78 81
7 98 90 92 93 76 78 82
8 97 91 92 92 75 80 82
9 98 91 93 93 75 79 80
10 97 90 92 92 73 80 82
11 98 92 93 93 76 78 82
12 98 91 93 93 74 77 80
13 98 91 93 93 75 78 80
14 98 90 92 92 74 80 82
15 98 91 92 92 76 79 82
in adults or urinary tract infections in children or adults [11].
The overall frequency of E. coli Kl observed in this study (12.5%) is similar to the results of other investigations [12, 13]. Fünfstück et al. [14] have shown that 14% E. coli strains isolated from the urine of patients with non-obstructive chronic pyelonephritis possessed K1 antigen. Slightly high-er phigh-ercentage of E. coli rods with K1 polysaccha-ride capsule (17%) was found by Devine et al. [8] and Evans et al. [15]. Czirok et al. [16] reported only 7.3% of urinary E. coli isolates carried the K1 antigen.
It has frequently been assumed that antibiotics used at sub-MICs might have an influence on the composition of the cell surface of gram-negative bacteria [4, 6, 17]. In this study, the authors in-vestigated the influence of sub-MICs of amikacin and ciprofloxacin on the presence of cell-surface K1 antigen of uropathogenic E. coli strains and their phagocytosis by neutrophils. The authors found that these antibiotics reduced amount of
E. coli clones possessing polysaccharide capsule. Own findings are consistent with those reported
by raponi et al. [18], who described a reduction in capsular material after exposure of E. coli rods to sub-MICs of netilmicin, ciprofloxacin, and flerox-acin. Suerbaum et al. [19] found a dose-dependent reduction of Kl production under the influence of imipenem, cephaloridine, and ciprofloxacin. Also Taylor et al. [20] and Kadurugamuwa et al. [21] observed an influence of antibiotics on the pro-duction of capsular polysaccharides in E. coli and
Klebsiella pneumoniae strains. Taylor et al. [20] found that treatment of E. coli cells with mecilli-nam caused a reduction of the extractable amount of Kl. Similarly Kadurugamuwa et al. [21] reported that various cephalosporins decreased the forma-tion of capsule by iron-depleted K. pneumoniae. The effects of sub-MICs of penicillin or clindamy-cin were evaluated in Streptococcus pneumoniae
isolates [22]. Clindamycin appears to be superior to penicillin in reducing the expression of the capsule by S. pneumoniae. After incubation in one-half of the MIC of clindamycin, 17.5% of isolates retained a capsule, compared to 87.5% after incubation with one-half of the MIC of penicillin. Brook et al. [23] showed that the exposure of S. pneumoniae to
Table 3. Effect of sub-MICs of amikacin on phagocytosis of E. coli rods by neutrophils. Phagocytotic indexes marked with asterix present statistically significant change with respect to the control value (without antibiotic), p< 0.05
Tabela 3. Wpływ stężeń subinhibicyjnych amikacyny na fagocytozę pałeczek E. coli przez neutrofile. Wartości indeksów fagocytarnych oznaczone gwiazdką są statystycznie istotne w odniesieniu do grupy kontrolnej (bez antybiotyku), p< 0,05
E. coli strains
(Szczepy E. coli) Phagocytic index (± SD)(Indeks fagocytarny)
without antibiotic sub-MICs of amikacin
1/2 1/4 1/8
1 10.8 ± 1.7 16.0 ± 1.5* 13.8 ± 1.4 13.5 ± 1.7
2 10.2 ± 1.6 15.9 ± 1.4* 13.8 ± 1.4 13.2 ± 1.4
3 10.7 ± 1.5 15.8 ± 1.5* 13.4 ± 1.5 12.8 ± 1.4
4 11.0 ± 1.8 16.2 ± 1.5* 14.2 ± 1.7* 13.2 ± 1.3
5 10.9 ± 1.8 15.6 ± 1.7* 13.4 ± 1.6 13.4 ± 1.6
6 12.0 ± 1.7 15.9 ± 1.8* 13.8 ± 1.8 13.2 ± 1.6
7 12.2 ± 1.8 16.0 ± 1.5* 14.9 ± 1.7* 13.4 ± 1.7
8 11.7 ± 1.7 14.2 ± 1.5* 13.8 ± 1.8 13.6 ± 1.8
9 11.5 ± 1.8 14.4 ± 1.4* 13.3 ± 1.8 12.8 ± 1.8
10 11.6 ± 1.6 14.8 ± 1.5* 13.2 ± 1.4 13.0 ± 1.5
11 11.1 ± 1.8 15.1 ± 1.7* 14.0 ± 1.5* 13.6 ± 1.6
12 11.5 ± 1.8 14.8 ± 1.8* 13.4 ± 1.5 12.8 ± 1.7
13 11.1 ± 1.8 15.8 ± 1.7* 13.7 ± 1.3 13.4 ± 1.8
14 11.4 ± 1.8 15.3 ± 1.7 * 13.9 ± 1.3 13.8 ± 1.6
Table 4. Effect of sub-MICs of ciprofloxacin on phagocytosis of E. coli rods by neutrophils. Phagocytotic indexes marked with asterix present statistically significant change with respect to the control value (without antibiotic), p< 0.05
Tabela 4.Wpływ stężeń subinhibicyjnych ciprofloksacyny na fagocytozę pałeczek E. coli przez neutrofile. Wartości indeksów fagocytarnych oznaczone gwiazdką są statystycznie istotne w odniesieniu do grupy kontrolnej (bez antybiotyku), p< 0,05
E. coli strains
(szczepy E. coli) Phagocytic index ( ± SD)(Indeks fagocytarny)
without antibiotic sub-MICs of ciprofloxacin
1/2 1/4 1/8
1 10.8 ± 1.7 18.9 ± 1.4* 15.4 ± 1.4* 14.2 ± 1.4
2 10.2 ± 1.6 17.2 ± 1.5* 14.3 ± 1.4* 13.8 ± 1.5
3 10.7 ± 1.5 18.3 ± 1.5* 14.2 ± 1.7* 13.4 ± 1.4
4 11.0 ± 1.8 19.0 ± 1.6* 14.7 ± 1.7* 13.6 ± 1.3
5 10.9 ± 1.8 19.2 ± 1.5* 14.8 ± 1.6* 14.2 ± 1.3*
6 12.0 ± 1.7 18.6 ± 1.5* 15.3 ± 1.4* 14.8 ± 1.4
7 12.2 ± 1.8 17.6 ± 1.7* 14.8 ± 1.4* 13.9 ± 1.6
8 11.7 ± 1.7 17.3 ± 1.8* 15.3 ± 1.7* 14.7 ± 1.7
9 11.5 ± 1.8 17.8 ± 1.7* 15.6 ± 1.8* 14.6 ± 1.7
10 11.6 ± 1.6 17.8 ± 1.5* 14.3 ± 1.8* 13.9 ± 1.8
11 11.1 ± 1.8 19.0 ± 1.5* 14.7 ± 1.5* 13.9 ± 1.5
12 11.5 ± 1.8 18.7 ± 1.6* 14.2 ± 1.7* 13.4 ± 1.5
13 11.1 ± 1.8 18.4 ± 1.7* 15.3 ± 1.4* 14.7 ± 1.6
14 11.4( ± 1.8) 18.2 ± 1.3* 15.6 ± 1.4* 14.1 ± 1.7
15 11.6( ± 1.7) 18.5 ± 1.4* 15.8 ± 1.5* 14.1 ± 1.4
Fig. 1. Microscopic appearance of phagocytic ingestion of E. coli cells grown: (a) in the absence of antibiotic, (b) in the presence of 1/2 of MIC of ciprofloxacin. Magnification ×1000 (arrow points to the ingested bacteria)
Ryc. 1. Mikroskopowy obraz sfagocytowanych komórek E. coli rosnących: (a) bez antybiotyku, (b) w obecności 1/2 MIC ciprofloksacyny. Powiększenie ×1000 (strzałka wskazuje sfagocytowane bakterie)
telithromycin at 1/2 of MIC commonly suppressed the formation of the capsule, whereas a sub-MIC of penicillin was less effective in this aspect.
Several studies indicate that capsular polysac-charides have antiphagocytic activity and suggest
hydrophilic nature, negatively charged character but also by serving as camouflage and masking the underlying opsonized surface [24–26].
The results of own study confirmed that strains that possessed lower amounts of clones with K an-tigen were more sensitive to phagocytosis. Adinolfi et al. [27] observed that phagocytosis after treat-ment with sub-MICs of imipenem or piperacil-lin was significantly higher compared to bacteria unexposed to antibiotics. Pretreatment with the β-lactam antibiotics rendered Staphylococcus au-reus more liable to phagocytosis. Also the values of phagocytic index were lower after the exposure of
E. coli strains to sub-MICs of gatifloxacin [28].
Presumably the exposure of bacteria to antibi-otics leads to changes in the surface components, altering among others, the hydrophilic character of surface into hydrophobic one, which contrib-utes to enhanced bacterial uptake by granulocytes and monocytes. The loss of antigen K1 facilitates the interaction between the specific antibody and complement component C3 associated with the outer membrane of bacteria and their receptors on phagocytic cells.
In conclusion, sub-MICs of amikacin and cip-rofloxacin interfere with the assembly of Kl capsu-lar polysaccharide of encapsulated E. coli, leading to an increase in phagocytic index.
Fig. 2. Comparison of the influence of sub-MICs of amikacin and ciprofloxacin on E. coli K1 rods in regards to: the percentage of clones susceptible to phage K1A (white bars) and phagocytic index (grey bars). Numbers over bars rep-resent percentage of clones, numbers on grey bars reprep-resent phagocytic index. The results are average values derived from all examined E. coli strains. Abbreviations: AN – amikacin, CIP – ciprofloxacin
Ryc. 2. Porównanie wpływu działania sub-MICs amikacyny i ciprofloksacyny na pałeczki E. coli K1 w odniesieniu do: odsetka klonów szczepów E. coli wrażliwych na faga K1A (białe słupki) i indeksu fagocytarnego (szare słupki). Liczby nad słupkami odpowiadają odsetkowi klonów, liczby na szarych słupkach są wartościami indeksów fagocytar-nych. Przedstawione dane są średnimi wartościami wyników pochodzących od wszystkich badanych szczepów E. coli. Skróty: AN – amikacyna, CIP – ciprofloksacyna
11.28 15.29 13.76 13.3 18.3 14.95 14.08
97.73
90.8 92.4 94.6
74.73 79.06
81.4
0 2 4 6 8 10 12 14 16 18 20
control 1/2AN 1/4AN 1/8AN 1/2CIP 1/4CIP 1/8CIP
value of phagocytic inde
x
wartość indeksu fagocytarnego
0 20 40 60 80 100 120
% clones sensitive to phage K1
A
% klonów wrażliwych na faga K1
A
v
grupa kontrolna
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Address for correspondence:
Dorota Wojnicz
Department of Biology and Medical Parasitology Wroclaw Medical University
Mikulicza-radeckiego 9 50-367 Wrocław Poland
Tel.: + 48 71 784 15 12
E-mail: [email protected]
Conflict of interest: None declared