Replication Dynamics for Six Gram-Negative Bacterial Species during Bloodstream Infection

ABSTRACT Bloodstream infections (BSI) are a major public health burden due to high mortality rates and the cost of treatment. The impact of BSI is further compounded by a rise in antibiotic resistance among Gram-negative species associated with these infections. Escherichia coli, Serratia marcescens...

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Autores principales:	Mark T. Anderson, Aric N. Brown, Ali Pirani, Sara N. Smith, Amanda L. Photenhauer, Yuang Sun, Evan S. Snitkin, Michael A. Bachman, Harry L. T. Mobley
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	bacteremia growth rate bloodstream infection generation time Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ddd4a91eb3004209a0e9be83e9243df5
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spelling	oai:doaj.org-article:ddd4a91eb3004209a0e9be83e9243df52021-11-10T18:37:50ZReplication Dynamics for Six Gram-Negative Bacterial Species during Bloodstream Infection10.1128/mBio.01114-212150-7511https://doaj.org/article/ddd4a91eb3004209a0e9be83e9243df52021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01114-21https://doaj.org/toc/2150-7511ABSTRACT Bloodstream infections (BSI) are a major public health burden due to high mortality rates and the cost of treatment. The impact of BSI is further compounded by a rise in antibiotic resistance among Gram-negative species associated with these infections. Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, Enterobacter hormaechei, Citrobacter freundii, and Acinetobacter baumannii are all common causes of BSI, which can be recapitulated in a murine model. The objective of this study was to characterize infection kinetics and bacterial replication rates during bacteremia for these six pathogens to gain a better understanding of bacterial physiology during infection. Temporal observations of bacterial burdens of the tested species demonstrated varied abilities to establish colonization in the spleen, liver, or kidney. K. pneumoniae and S. marcescens expanded rapidly in the liver and kidney, respectively. Other organisms, such as C. freundii and E. hormaechei, were steadily cleared from all three target organs throughout the infection. In situ replication rates measured by whole-genome sequencing of bacterial DNA recovered from murine spleens demonstrated that each species was capable of sustained replication at 24 h postinfection, and several species demonstrated <60-min generation times. The relatively short generation times observed in the spleen were in contrast to an overall decrease in bacterial burden for some species, suggesting that the rate of immune-mediated clearance exceeded replication. Furthermore, bacterial generation times measured in the murine spleen approximated those measured during growth in human serum cultures. Together, these findings provide insight into the infection kinetics of six medically important species during bacteremia. IMPORTANCE Bloodstream infections are a global public health problem. The goal of this work was to determine the replication characteristics of Gram-negative bacterial species in the host following bloodstream infection. The number of bacteria in major organs is likely determined by a balance between replication rates and the ability of the host to clear bacteria. We selected a cohort of six species from three families that represent common causative agents of bloodstream infections in humans and determined their replication rates in a murine bacteremia model. We found that the bacteria grow rapidly in the spleen, demonstrating that they can obtain the necessary nutrients for growth in this environment. However, the overall number of bacteria decreased in most cases, suggesting that killing of bacteria outpaces their growth. Through a better understanding of how bacteria replicate during bloodstream infections, we aim to gain insight into future means of combating these infections.Mark T. AndersonAric N. BrownAli PiraniSara N. SmithAmanda L. PhotenhauerYuang SunEvan S. SnitkinMichael A. BachmanHarry L. T. MobleyAmerican Society for Microbiologyarticlebacteremiagrowth ratebloodstream infectiongeneration timeMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacteremia growth rate bloodstream infection generation time Microbiology QR1-502
spellingShingle	bacteremia growth rate bloodstream infection generation time Microbiology QR1-502 Mark T. Anderson Aric N. Brown Ali Pirani Sara N. Smith Amanda L. Photenhauer Yuang Sun Evan S. Snitkin Michael A. Bachman Harry L. T. Mobley Replication Dynamics for Six Gram-Negative Bacterial Species during Bloodstream Infection
description	ABSTRACT Bloodstream infections (BSI) are a major public health burden due to high mortality rates and the cost of treatment. The impact of BSI is further compounded by a rise in antibiotic resistance among Gram-negative species associated with these infections. Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, Enterobacter hormaechei, Citrobacter freundii, and Acinetobacter baumannii are all common causes of BSI, which can be recapitulated in a murine model. The objective of this study was to characterize infection kinetics and bacterial replication rates during bacteremia for these six pathogens to gain a better understanding of bacterial physiology during infection. Temporal observations of bacterial burdens of the tested species demonstrated varied abilities to establish colonization in the spleen, liver, or kidney. K. pneumoniae and S. marcescens expanded rapidly in the liver and kidney, respectively. Other organisms, such as C. freundii and E. hormaechei, were steadily cleared from all three target organs throughout the infection. In situ replication rates measured by whole-genome sequencing of bacterial DNA recovered from murine spleens demonstrated that each species was capable of sustained replication at 24 h postinfection, and several species demonstrated <60-min generation times. The relatively short generation times observed in the spleen were in contrast to an overall decrease in bacterial burden for some species, suggesting that the rate of immune-mediated clearance exceeded replication. Furthermore, bacterial generation times measured in the murine spleen approximated those measured during growth in human serum cultures. Together, these findings provide insight into the infection kinetics of six medically important species during bacteremia. IMPORTANCE Bloodstream infections are a global public health problem. The goal of this work was to determine the replication characteristics of Gram-negative bacterial species in the host following bloodstream infection. The number of bacteria in major organs is likely determined by a balance between replication rates and the ability of the host to clear bacteria. We selected a cohort of six species from three families that represent common causative agents of bloodstream infections in humans and determined their replication rates in a murine bacteremia model. We found that the bacteria grow rapidly in the spleen, demonstrating that they can obtain the necessary nutrients for growth in this environment. However, the overall number of bacteria decreased in most cases, suggesting that killing of bacteria outpaces their growth. Through a better understanding of how bacteria replicate during bloodstream infections, we aim to gain insight into future means of combating these infections.
format	article
author	Mark T. Anderson Aric N. Brown Ali Pirani Sara N. Smith Amanda L. Photenhauer Yuang Sun Evan S. Snitkin Michael A. Bachman Harry L. T. Mobley
author_facet	Mark T. Anderson Aric N. Brown Ali Pirani Sara N. Smith Amanda L. Photenhauer Yuang Sun Evan S. Snitkin Michael A. Bachman Harry L. T. Mobley
author_sort	Mark T. Anderson
title	Replication Dynamics for Six Gram-Negative Bacterial Species during Bloodstream Infection
title_short	Replication Dynamics for Six Gram-Negative Bacterial Species during Bloodstream Infection
title_full	Replication Dynamics for Six Gram-Negative Bacterial Species during Bloodstream Infection
title_fullStr	Replication Dynamics for Six Gram-Negative Bacterial Species during Bloodstream Infection
title_full_unstemmed	Replication Dynamics for Six Gram-Negative Bacterial Species during Bloodstream Infection
title_sort	replication dynamics for six gram-negative bacterial species during bloodstream infection
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/ddd4a91eb3004209a0e9be83e9243df5
work_keys_str_mv	AT marktanderson replicationdynamicsforsixgramnegativebacterialspeciesduringbloodstreaminfection AT aricnbrown replicationdynamicsforsixgramnegativebacterialspeciesduringbloodstreaminfection AT alipirani replicationdynamicsforsixgramnegativebacterialspeciesduringbloodstreaminfection AT saransmith replicationdynamicsforsixgramnegativebacterialspeciesduringbloodstreaminfection AT amandalphotenhauer replicationdynamicsforsixgramnegativebacterialspeciesduringbloodstreaminfection AT yuangsun replicationdynamicsforsixgramnegativebacterialspeciesduringbloodstreaminfection AT evanssnitkin replicationdynamicsforsixgramnegativebacterialspeciesduringbloodstreaminfection AT michaelabachman replicationdynamicsforsixgramnegativebacterialspeciesduringbloodstreaminfection AT harryltmobley replicationdynamicsforsixgramnegativebacterialspeciesduringbloodstreaminfection
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Replication Dynamics for Six Gram-Negative Bacterial Species during Bloodstream Infection

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