A functional tonB gene is required for both virulence and competitive fitness in a chinchilla model of Haemophilus influenzae otitis media

Morton, Daniel J.; Hempel, Randy J.; Seale, Thomas W.; Whitby, Paul W.; Stull, Terrence L.

doi:10.1186/1756-0500-5-327

Cited by 24 publications

(24 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The TonB system of H. influenzae is involved in iron uptake mechanisms and is essential for virulence (Jarosik et al, 1995;Morton et al, 2012). Several pathogens also secrete high affinity iron-binding siderophores for iron retrieval from the surrounding tissue (Andrews et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Haemophilus influenzae stores and distributes hemin by using Protein E

Jubair

Singh

Fleury

et al. 2014

International Journal of Medical Microbiology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Haemophilus influenzae stores and distributes hemin by using Protein E

Jubair

Singh

Fleury

et al. 2014

International Journal of Medical Microbiology

View full text Add to dashboard Cite

“…Chinchilla has been used as a common animal model in auditory research for developing AOM model through transbullar injection of bacteria such as Haemophilus influenzae [2,[8][9][10][11]]. The infection induced by H. influenzae in the chinchilla middle ear causes middle ear pressure, middle ear effusion, and structural changes in the ear tissues as reported by Guan et al [2].…”

Section: Introductionmentioning

confidence: 96%

Dynamic Properties of Tympanic Membrane in a Chinchilla Otitis Media Model Measured With Acoustic Loading

Yokell

Wang

Gan

2015

Journal of Biomechanical Engineering

View full text Add to dashboard Cite

Otitis media is the most common infectious disease in young children, which results in changes in the thickness and mechanical properties of the tympanic membrane (TM) and induces hearing loss. However, there are no published data for the dynamic properties of the TM in otitis media ears, and it is unclear how the mechanical property changes are related to TM thickness variation. This paper reports a study of the measurement of the dynamic properties of the TM in a chinchilla acute otitis media (AOM) model using acoustic loading and laser Doppler vibrometry (LDV). AOM was created through transbullar injection of Haemophilus influenzae into the middle ear, and AOM samples were prepared 4 days after inoculation. Vibration of the TM specimen induced by acoustic loading was measured via LDV over a frequency range of 0.1-8 kHz. The experiment was then simulated in a finite element (FE) model, and the inverse-problem solving method was used to determine the complex modulus in the frequency domain. Results from 12 ears (six control and six AOM) show that the storage modulus of the TM from AOM ears was on average 53% higher than that of control ears, while the loss factor was 17.3% higher in control ears than in AOM ears at low-frequency (f < 1 kHz). At high-frequency (e.g., 8000 Hz), there was a mean 40% increase in storage modulus of the TM from AOM compared to control samples. At peak frequency (e.g., 3 kHz), there was a 19.5% increase in loss factor in control samples compared to AOM samples. These findings quantify the changes induced by AOM in the chinchilla TM, namely, a significant increase in both the storage and loss moduli.

show abstract

“…We propose that the dynamic association and dissociation of TonB 2 -ExbB 4 and ExbD 2 -ExbB 4 complexes during energy transduction is accomplished through modulation of the ExbB cytoplasmic domains, which constitute the majority of its soluble residues (40,73). The most speculative part of our model combines the ExbB 4 from TonB 2 and ExbD 2 into ExbB 8 as scaffolding for a dimer of carboxy-terminal heterodimers, since it appears that they subsequently revert back to their original condition as separate TonB 2 -ExbB 4 and ExbD 2 -ExbB 4 complexes to initiate a new cycle of energy transduction.…”

Section: Figmentioning

confidence: 99%

“…8). Their previous isolation of ExbB 4 -ExbD 2 complexes in vitro (52) could reflect the pool of ExbD 2 homodimers that are not in contact with TonB 2 in Fig. 8.…”

Section: Figmentioning

confidence: 99%

See 1 more Smart Citation

From Homodimer to Heterodimer and Back: Elucidating the TonB Energy Transduction Cycle

2015

View full text Add to dashboard Cite

The TonB system actively transports large, scarce, and important nutrients through outer membrane (OM) transporters of Gram-negative bacteria using the proton gradient of the cytoplasmic membrane (CM). In Escherichia coli, the CM proteins ExbB and ExbD harness and transfer proton motive force energy to the CM protein TonB, which spans the periplasmic space and cyclically binds OM transporters. TonB has two activity domains: the amino-terminal transmembrane domain with residue H20 and the periplasmic carboxy terminus, through which it binds to OM transporters. TonB is inactivated by all substitutions at residue H20 except H20N. Here, we show that while TonB trapped as a homodimer through its amino-terminal domain retained full activity, trapping TonB through its carboxy terminus inactivated it by preventing conformational changes needed for interaction with OM transporters. Surprisingly, inactive TonB H20A had little effect on homodimerization through the amino terminus and instead decreased TonB carboxy-terminal homodimer formation prior to reinitiation of an energy transduction cycle. That result suggested that the TonB carboxy terminus ultimately interacts with OM transporters as a monomer. Our findings also suggested the existence of a separate equimolar pool of ExbD homodimers that are not in contact with TonB. A model is proposed where interaction of TonB homodimers with ExbD homodimers initiates the energy transduction cycle, and, ultimately, the ExbD carboxy terminus modulates interactions of a monomeric TonB carboxy terminus with OM transporters. After TonB exchanges its interaction with ExbD for interaction with a transporter, ExbD homodimers undergo a separate cycle needed to re-energize them. IMPORTANCECanonical mechanisms of active transport across cytoplasmic membranes employ ion gradients or hydrolysis of ATP for energy. Gram-negative bacterial outer membranes lack these resources. The TonB system embodies a novel means of active transport across the outer membrane for nutrients that are too large, too scarce, or too important for diffusion-limited transport. A proton gradient across the cytoplasmic membrane is converted by a multiprotein complex into mechanical energy that drives high-affinity active transport across the outer membrane. This system is also of interest since one of its uses in pathogenic bacteria is for competition with the host for the essential element iron. Understanding the mechanism of the TonB system will allow design of antibiotics targeting iron acquisition.T he ability to acquire iron is the basis of a tug-of-war between host and bacterial pathogen (1, 2). Successful pathogens can acquire iron from their hosts, and in the case of Gram-negative bacteria, that is usually mediated by the TonB system, thus making the understanding of its mechanism an imperative goal (3, 4) and an attractive target for antibiotic development (5).In broad terms, the TonB system harnesses the proton motive force (PMF) of the cytoplasmic membrane (CM) to energize active transport across a ...

show abstract

A functional tonB gene is required for both virulence and competitive fitness in a chinchilla model of Haemophilus influenzae otitis media

Cited by 24 publications

References 32 publications

Haemophilus influenzae stores and distributes hemin by using Protein E

Haemophilus influenzae stores and distributes hemin by using Protein E

Dynamic Properties of Tympanic Membrane in a Chinchilla Otitis Media Model Measured With Acoustic Loading

From Homodimer to Heterodimer and Back: Elucidating the TonB Energy Transduction Cycle

Contact Info

Product

Resources

About