The microbial load and the severity of morphological changes in the prostate during infection with various titers of uropathogens: a comparison of data from an animal model study
Authors: Kogan M. I. , Ismailov R. S. , Todorov S. S. , Naboka Yu. L. , Gudima I. A. 
Published: October 2022

Introduction. It has been established in an animal model that coagulase-negative staphylococci (Staphylococcus haemolyticus) and anaerobes (Peptococcus niger) cause the development of an acute inflammatory process in the prostate when inoculated with 103 CFU/ml. At the same time, data have been published indicating the pathogenic potential of these microorganisms on a titer of 102 CFU/ml. But it was confirmed for the model of acute obstructive pyelonephritis. In addition, the characteristics of the formation of the inflammatory response at different times were determined, which require detailed verification and comparative characteristics with those during infection with a causative uropathogen (Escherichia coli).

Objective. Based on the results of the experiment, to carry out: 1) an evaluation of the relationship between the dynamics of microbial load and the degree of pathomorphological changes in prostate tissues during infection with various uropathogens in a titer of 103 CFU/ml; 2) an evaluation of the degree of microbial load and severity of histological changes in prostate tissues on follow-up day 7 with transurethral infection with various uropathogens in a subpathogenic titer of 102 CFU/ml; 3) a fundamental comparative analysis of the indicators of contamination and the severity of inflammatory changes on follow-up day 7 after the inoculation of various uropathogens in titers of 102 and 103 CFU/ml.

Materials and methods. The animal model was performed using the FELASA and ARRIVE guidelines. Lab animals: 20 New Zealand rabbits. Uropathogens: E. coli, S. haemolyticus, and P. niger. Infectious titers: 102.3 cfu/ml. Uropathogen inoculation technique: topical transurethral. Randomization: all laboratory animals were divided into 4 groups depending on the uropathogen (3 experimental, 1 control). Follow-up periods: day 1, 3, 7 and 14 for a titer of 103 CFU/ml, and day 7 for a titer of 102 CFU/ml. At the end of the follow-up, euthanasia and autopsy were performed with the extraction of the urogenital organ complex. Hereafter, biopsies were taken from various parts of the prostate. Cultural and histological studies of prostate tissues were carried out using standard methods. The results were analyzed using Statistica 10.2 (StatSoft Inc., Tulsa, OK, USA) and GraphPad Prism 9 (GraphPad Software Inc., Graphpad Holdings LLC, San Diego, CA, USA) programs through descriptive and nonparametric statistics.

Results. Bacterial contamination of prostate tissue was determined in all cases of infection with differences (p < 0.05) in some indicators between the E. coli and P. niger groups at different observation periods, but only in the case of inoculation of the test titer of 103 CFU/ml. Histological evaluation of prostate tissues after inoculation with 103 CFU/ml verified the presence of acute destructive changes in the prostate from the follow-up day 1, which were more pronounced in the S. haemolyticus and E. coli groups. However, similar characteristics of the development of the inflammatory process in the form of hyper-eosinophilic infiltration in the early stages and pronounced congestion of the prostatic glands were identified in the S. haemolyticus and P. niger groups. Comparison of trends in dynamic changes of microbial load (rise / decline) and severity of pathological changes (increase / resolution) in prostate tissues in established follow-up periods showed the presence of relative synchronization of trends (from days 1 to 7) in the S. haemolyticus and P. niger groups, and complete synchronization in the E. coli group. When comparing the median microbial load of the prostate on the follow-up day 7, no intergroup (p > 0.05) differences were found both in cases of infection with a titer of 103 CFU/ml, and when compared with the data on contamination for a test titer of 102 CFU/ml, at the same time observations. At once, when E. coli and S. haemolyticus were infected at a subpathogenic titer of 102 CFU/ml, inflammatory changes were recorded that had a mild diffuse character, in relation to those after inoculation of these pathogens in a titer of 103 CFU/ml. In turn, P. niger induced the development of low-intensity focal alteration in isolated areas of prostate tissues.

Conclusions. Detailed analysis of culture and histological data showed that E. coli, S. haemolyticus and P. niger have significant pathogenic potential at titer of 103 CFU/ml. In turn, when the titer decreases to 102 CFU/ml, E. coli and S. haemolyticus retain their pathogenic potential, but the severity of the inflammatory reaction is significantly reduced. It was also found that a change in bacterial contamination affects the severity of the inflammatory process in all groups during seven follow-up days at a given test titer.