Dietary restriction of iron availability attenuates UPEC pathogenesis in a mouse model of urinary tract infection

Bauckman, Kyle; Matsuda, Rina; Higgins, Cassandra B.; DeBosch, Brian J.; Wang, Caihong; Mysorekar, Indira U.

doi:10.1152/ajprenal.00133.2018

Cited by 27 publications

(24 citation statements)

References 62 publications

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“…Our data reveal the presence of eight genes (two hlyABCD operons) involved in transport, activation, and secretion of hemolysin both in the BH100 strain and in the E coli 536 while, as expected, no hemolysin related gene was found in K-12. Recent studies have reported iron uptake genes as being vital in the pathogenesis of UPEC strains to overcome the scarcity of iron (Robinson et al, 2018 ; Bauckman et al, 2019 ). Interestingly, three siderophore genes were found in the E. coli strains 536 and BH100 MG2014 but none in the K-12.…”

Section: Resultsmentioning

confidence: 99%

Genomic Characterization of Multidrug-Resistant Escherichia coli BH100 Sub-strains

et al. 2021

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The rapid emergence of multidrug-resistant (MDR) bacteria is a global health problem. Mobile genetic elements like conjugative plasmids, transposons, and integrons are the major players in spreading resistance genes in uropathogenic Escherichia coli (UPEC) pathotype. The E. coli BH100 strain was isolated from the urinary tract of a Brazilian woman in 1974. This strain presents two plasmids carrying MDR cassettes, pBH100, and pAp, with conjugative and mobilization properties, respectively. However, its transposable elements have not been characterized. In this study, we attempted to unravel the factors involved in the mobilization of virulence and drug-resistance genes by assessing genomic rearrangements in four BH100 sub-strains (BH100 MG2014, BH100 MG2017, BH100L MG2017, and BH100N MG2017). Therefore, the complete genomes of the BH100 sub-strains were achieved through Next Generation Sequencing and submitted to comparative genomic analyses. Our data shows recombination events between the two plasmids in the sub-strain BH100 MG2017 and between pBH100 and the chromosome in BH100L MG2017. In both cases, IS3 and IS21 elements were detected upstream of Tn21 family transposons associated with MDR genes at the recombined region. These results integrated with Genomic island analysis suggest pBH100 might be involved in the spreading of drug resistance through the formation of resistance islands. Regarding pathogenicity, our results reveal that BH100 strain is closely related to UPEC strains and contains many IS3 and IS21-transposase-enriched genomic islands associated with virulence. This study concludes that those IS elements are vital for the evolution and adaptation of BH100 strain.

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Section: Resultsmentioning

confidence: 99%

Genomic Characterization of Multidrug-Resistant Escherichia coli BH100 Sub-strains

et al. 2021

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“…Treatment with a low iron diet decreased local bladder tissue iron stores and reduced bacterial colonization and inflammation. Furthermore, hepcidin-deficient mice ( Hamp1 −/− ) exhibited an accumulation in iron deposits and significantly higher bacterial colonization and heightened inflammatory response to the UTI [ 61 ]. Lastly, studies by Hagan and colleagues (2010) also demonstrate the importance of iron in UPEC pathogenesis.…”

Section: Local Infectionmentioning

confidence: 99%

Iron Chelation in Local Infection

et al. 2021

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Iron is an essential element in multiple biochemical pathways in humans and pathogens. As part of the innate immune response in local infection, iron availability is restricted locally in order to reduce overproduction of reactive oxygen species by the host and to attenuate bacterial growth. This physiological regulation represents the rationale for the therapeutic use of iron chelators to support induced iron deprivation and to treat infections. In this review paper we discuss the importance of iron regulation through examples of local infection and the potential of iron chelation in treating infection.

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“…Therefore, interpretation of rUTIs must be updated to include the possibility that metal exposure from inhalation, diet, and cosmetics are potential risk factors for UTIs onset and recurrence. On the other hand, mitigation of urinary levels of heavy metals may prove to be an alternative treatment to rUTIs by depriving pathogens use of essential metals or nutrients in comparison to antibiotic usage (Subashchandrabose and Mobley, 2015;Bauckman et al, 2019).…”

Section: Impact Of Dietary Transition Metals On Uti Pathophysiologymentioning

confidence: 99%

“…Free iron (Fe) is necessary for most biological processes such as cellular respiration, DNA replication, and oxygen transport via hemoglobin. Therefore, there is an intense competition between the host and pathogens for Fe, Fe deprivation from uropathogens may be a primary mechanism to mitigate virulence (Subashchandrabose and Mobley, 2015;Bauckman et al, 2019). For E. coli pathogenesis, invasion and disruption of the host urothelium to increase the availability of free Fe 2+ /Fe 3+ is essential to initiate and maintain virulence (Gao et al, 2012).…”

Section: Impact Of Dietary Transition Metals On Uti Pathophysiologymentioning

confidence: 99%

Recurrent Urinary Tract Infections: Unraveling the Complicated Environment of Uncomplicated rUTIs

Krogh

Rettig

Lyng

et al. 2021

Front. Cell. Infect. Microbiol.

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Urinary tract infections (UTIs) are frequent in humans, affecting the upper and lower urinary tract. Present diagnosis relies on the positive culture of uropathogenic bacteria from urine and clinical markers of inflammation of the urinary tract. The bladder is constantly challenged by adverse environmental stimuli which influence urinary tract physiology, contributing to a dysbiotic environment. Simultaneously, pathogens are primed by environmental stressors such as antibiotics, favoring recurrent UTIs (rUTIs), resulting in chronic illness. Due to different confounders for UTI onset, a greater understanding of the fundamental environmental mechanisms and microbial ecology of the human urinary tract is required. Such advancements could promote the tandem translation of bench and computational studies for precision treatments and clinical management of UTIs. Therefore, there is an urgent need to understand the ecological interactions of the human urogenital microbial communities which precede rUTIs. This review aims to outline the mechanistic aspects of rUTI ecology underlying dysbiosis between both the human microbiome and host physiology which predisposes humans to rUTIs. By assessing the applications of next generation and systems level methods, we also recommend novel approaches to elucidate the systemic consequences of rUTIs which requires an integrated approach for successful treatment. To this end, we will provide an outlook towards the so-called ‘uncomplicated environment of UTIs’, a holistic and systems view that applies ecological principles to define patient-specific UTIs. This perspective illustrates the need to withdraw from traditional reductionist perspectives in infection biology and instead, a move towards a systems-view revolving around patient-specific pathophysiology during UTIs.

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Dietary restriction of iron availability attenuates UPEC pathogenesis in a mouse model of urinary tract infection

Cited by 27 publications

References 62 publications

Genomic Characterization of Multidrug-Resistant Escherichia coli BH100 Sub-strains

Genomic Characterization of Multidrug-Resistant Escherichia coli BH100 Sub-strains

Iron Chelation in Local Infection

Recurrent Urinary Tract Infections: Unraveling the Complicated Environment of Uncomplicated rUTIs

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