Uropathogenic Escherichia coli subverts mitochondrial metabolism to enable intracellular bacterial pathogenesis in urinary tract infection

Beebout, Connor J.; Robertson, Gabriella L.; Reinfeld, Bradley I.; Blee, Alexandra M.; Morales, Grace; Brannon, John R.; Chazin, Walter J.; Rathmell, W. Kimryn; Rathmell, Jeffrey C.; Gama, Vivian; Hadjifrangiskou, Maria

doi:10.1038/s41564-022-01205-w

Cited by 16 publications

(9 citation statements)

References 62 publications

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“…Meanwhile, urine was used as another real sample to evaluate the potential practice application of the constructed sensing system. Urinary tract infections (UTIs) are one of the most common bacterial infections . Urinary infections are related to diseases of cystitis, prostatitis, and pyelonephritis, which pose serious threats to human health .…”

Section: Resultsmentioning

confidence: 99%

“…Urinary tract infections (UTIs) are one of the most common bacterial infections. 55 Urinary infections are related to diseases of cystitis, prostatitis, and pyelonephritis, which pose serious threats to human health. 56 The detection range of E. coli via the developed CRET-based POCT sensing platform covers the positive threshold of 10 5 cfu mL −1 for UTI.…”

Section: Synthesis Characterization and Sensitized Ros Generation Of ...mentioning

confidence: 99%

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AIE Nanozyme-Based Long Persistent Chemiluminescence and Fluorescence for POCT of Pathogenic Bacteria

Fang

Tian

et al. 2023

ACS Sens.

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Pathogenic bacteria are widely distributed in diverse environments and significantly threaten human health. Point-of-care testing (POCT) is a valuable way for early warnings of bacteria threat. Herein, a chemiluminescence (CL)-based ratiometric sensing platform was constructed for sensitive POCT of bacteria according to a newly designed aggregation-induced emission (AIE) molecule. The new AIE molecule presents oxidase-like properties (named as AIEzyme) and can trigger long persistent CL of luminol (LUM) with strong intensity in the absence of H2O2. The CL emission can be monitored with the naked eye for over 2 h. The emission mechanism is explored and may be attributed to the persistent reactive oxygen species generation of the AIEzyme according to the cyclic energy transfer between the AIEzyme and luminol, which catalyzes CL of luminol. Based on the CL resonance energy transfer mechanism, an afterglow luminescence system is further developed, which is used to construct a ratiometric biosensor for detection of pathogenic bacteria. With a homemade holder as a detection room and a smartphone as an analyzer, the portable biosensing platform is used for quantitative POCT of bacteria in real samples with good recovery. The detection is free of H2O2 and an external excitation source, which not only simplifies the operation but reduces interference. Specifically, the long persistent luminescence and the ratiometric strategy can significantly improve accuracy, providing an instructive way for point-of-need analysis, for example, SARS-CoV-2 detection and bioimaging analysis.

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Section: Resultsmentioning

confidence: 99%

Section: Synthesis Characterization and Sensitized Ros Generation Of ...mentioning

confidence: 99%

AIE Nanozyme-Based Long Persistent Chemiluminescence and Fluorescence for POCT of Pathogenic Bacteria

Fang

Tian

et al. 2023

ACS Sens.

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“…In uropathogenic E. coli (UPEC), the deletion of cydAB resulted in reduced intracellular replication, oxygen consumption, nitric oxide tolerance, and extracellular acidification rates. Further, cydAB was shown to be involved in antagonizing pro-apoptotic factors and rewiring of host cell metabolism during UPEC infection of urothelial cells, and the amino acid lysine at position 252 in CydA was shown to be a key residue for bacterial respiration required for intracellular survival [ 43 ]. Consistent with these observations, we observed an increased expression of both cydA and cydB transcripts at 24 and 48 h, when compared to 3h post-infection ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 99%

A Small Non-Coding RNA Mediates Transcript Stability and Expression of Cytochrome bd Ubiquinol Oxidase Subunit I in Rickettsia conorii

Narra

Alsing

Sahni

et al. 2023

IJMS

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Small regulatory RNAs (sRNAs) are now widely recognized for their role in the post-transcriptional regulation of bacterial virulence and growth. We have previously demonstrated the biogenesis and differential expression of several sRNAs in Rickettsia conorii during interactions with the human host and arthropod vector, as well as the in vitro binding of Rickettsia conorii sRNA Rc_sR42 to bicistronic cytochrome bd ubiquinol oxidase subunits I and II (cydAB) mRNA. However, the mechanism of regulation and the effect of sRNA binding on the stability of the cydAB bicistronic transcript and the expression of the cydA and cydB genes are still unknown. In this study, we determined the expression dynamics of Rc_sR42 and its cognate target genes, cydA and cydB, in mouse lung and brain tissues during R. conorii infection in vivo and employed fluorescent and reporter assays to decode the role of sRNA in regulating cognate gene transcripts. Quantitative RT-PCR revealed significant changes in the expression of sRNA and its cognate target gene transcripts during R. conorii infection in vivo, and a greater abundance of these transcripts was observed in the lungs compared to brain tissue. Interestingly, while Rc_sR42 and cydA exhibited similar patterns of change in their expression, indicating the influence of sRNA on the mRNA target, the expression of cydB was independent of sRNA expression. Further, we constructed reporter plasmids of sRNA and cydAB bicistronic mRNA to decipher the role of sRNA on CydA and CydB expression. We observed increased expression of CydA in the presence of sRNA but detected no change in CydB expression in the presence or absence of sRNA. In sum, our results demonstrate that the binding of Rc_sR42 is required for the regulation of cydA but not cydB. Further studies on understanding the influence of this interaction on the mammalian host and tick vector during R. conorii infection are in progress.

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“…However, the intracellular environment is inadequate for the survival of UPEC. Therefore, several strategies were developed for the intracellular survival of UPEC, which are summarized in Table 3 , including (1) aerobic respiration to establish UTI by intracellular oxygen scavenging from the cytosol through cytochrome bd [ 43 ], the aim of which is to antagonize host apoptosis, thereby protecting intracellular uropathogens from the host cells’ exfoliation and supporting their replicative environment; (2) iron acquisition for cellular processes and bacterial growth by siderophores and/or other iron acquisition systems; the siderophores, known as yersiniabactin, salmochelin, enterobactin, and aerobactin, are capable of scavenging iron from the environment and further concentrating it in the bacterial cytosol. Different stains of UPEC have evolved iron acquisition systems to swipe iron from the host; furthermore, significantly higher levels of yersiniabactin and salmochelin were reported in UPEC than that in E.coli from the rectum, indicating their specific role in pathogenesis within the urinary tract [ 44 ]; (3) zinc acquisition by zinc-transport systems for iron hemostasis and relief of oxidative stress to maintain cellular function [ 45 ]; and (4) toxin secretion, which results in cytotoxic activity and destruction of the immune cells, further gaining access to nutrients from the hosts [ 14 ].…”

Section: Acute Uncomplicated Cystitismentioning

confidence: 99%

Emerging Non-Antibiotic Options Targeting Uropathogenic Mechanisms for Recurrent Uncomplicated Urinary Tract Infection

Chen

Lee

Chuang

2023

IJMS

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Urinary tract infections (UTIs) are the most frequent bacterial infections in the clinical setting. Even without underlying anatomic or functional abnormalities, more than 40% of women experience at least one UTI in their lifetime, of which 30% develop recurrent UTIs (rUTIs) within 6 months. Conventional management with antibiotics for rUTIs may eventually lead to the development of multidrug-resistant uropathogens. Targeting of the pathogenicity of rUTIs, the evolution of uropathogenic Escherichia coli (UPEC), and inadequate host defenses by immune responses should be explored to provide non-antibiotic solutions for the management of rUTIs. The adaptive evolution of UPEC has been observed in several aspects, including colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. Focusing on the antivirulence of UPEC and modulating the immunity of susceptible persons, researchers have provided potential alternative solutions in four categories: antiadhesive treatments (i.e., cranberries and D-mannose), immunomodulation therapies, vaccines, and prophylaxis with topical estrogen therapy and probiotics (e.g., Lactobacillus species). Combination therapies targeting multiple pathogenic mechanisms are expected to be a future trend in UTI management, although some of these treatment options have not been well established in terms of their long-term efficacy. Additional clinical trials are warranted to validate the therapeutic efficacy and durability of these techniques.

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Uropathogenic Escherichia coli subverts mitochondrial metabolism to enable intracellular bacterial pathogenesis in urinary tract infection

Cited by 16 publications

References 62 publications

AIE Nanozyme-Based Long Persistent Chemiluminescence and Fluorescence for POCT of Pathogenic Bacteria

AIE Nanozyme-Based Long Persistent Chemiluminescence and Fluorescence for POCT of Pathogenic Bacteria

A Small Non-Coding RNA Mediates Transcript Stability and Expression of Cytochrome bd Ubiquinol Oxidase Subunit I in Rickettsia conorii

Emerging Non-Antibiotic Options Targeting Uropathogenic Mechanisms for Recurrent Uncomplicated Urinary Tract Infection

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