Bacterial multispecies invasion of human epithelial bladder cells

Abstract

AbstractUrinary tract infections (UTI) are one of the most common bacterial infections worldwide. While the overall infection course is known on a macroscale, bacterial behavior is not fully understood at the cellular level and bacterial pathophysiology during multispecies infection is not well characterized. Here we establish co-infection models combined with high resolution imaging to compare single- and multi-species bladder cell invasion events in three common uropathogens: uropathogenicEscherichia coli(UPEC),Klebsiella pneumoniaeandEnterococcus faecalis. While all three species invaded the bladder cells, under flow conditions the Gram-positiveE. faecaliswas significantly less invasive compared to the Gram-negative UPEC andK. pneumoniae. When introduced simultaneously during an infection experiment, all three bacterial species sometimes invaded the same bladder cell, at differing frequencies suggesting complex interactions between bacterial species and bladder cells. Inside host cells, we observed encasement ofE. faecaliscolonies specifically by UPEC. During subsequent dispersal from the host cells, only the Gram-negative bacteria underwent infection-related filamentation (IRF). Taken together, our data suggest that bacterial multispecies invasions of single bladder cells are frequent and support earlier studies showing intraspecies cooperation on a biochemical level during UTI.