bioRxiv ScienceSearch

bioRxiv · 10.1101/2020.01.08.899740

Damage repair versus aging in biofilms

Abstract

The extent of senescence due to damage accumulation (or aging) is evidently evolvable as it varies hugely between species and is not universal, suggesting that its fitness advantages depend on life history and environment. In contrast, repair of damage is present in all organisms studied. Repair and segregation of damage have not always been considered as alternatives, despite the fundamental trade-off between investing resources into repair or growth. For unicellular organisms, unrepaired damage could be divided asymmetrically between daughter cells, leading to aging of one and rejuvenation of the other. Repair of unicells has been shown to be advantageous in well-mixed environments such as chemostats. However, most microorganisms live in spatially structured systems such as biofilms with gradients of environmental conditions and cellular physiology as well as clonal population structure. We asked whether this clonal structure might favor aging by damage segregation as this can be seen as a division of labor strategy, akin to the germline soma division in multicellular organisms. We used an individual-based model with a newly developed adaptive repair strategy where cells respond to their current intracellular damage levels by investing into repair machinery accordingly. We found that the new adaptive repair strategy was advantageous whenever efficient and optimal, both in biofilms and chemostats. Thus, biofilms do not favor a germline soma-like division of labor between daughter cells in terms of damage segregation. We suggest that damage segregation is only beneficial when active and effective, extrinsic mortality is high and a degree of multicellularity is present. IMPORTANCEDamage is an inevitable consequence of life, leading to a trade-off between allocating resources into damage repair or into growth whilst allowing aging, i.e., segregation of damage upon cell division. Few studies considered repair as an alternative to aging. Moreover, all previous studies merely considered well-mixed environments, although the vast majority of unicellular organisms live in spatially structured environments, exemplified by biofilms, and fitness advantages in well-mixed systems often turn into disadvantages in spatially structured systems. We compared the fitness consequences of aging versus damage repair in biofilms with an individual-based model implementing an adaptive repair mechanism based on sensing damage. We found that aging is not beneficial. Instead, it is useful as a stress response to deal with damage that failed to be repaired when (i) clearly asymmetric cell division is feasible; (ii) extrinsic mortality is high; and (iii) a degree of multicellularity is present.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Wright, R. J., Clegg, R. J., Coker, T. L., Kreft, J.-U.. 2020-01-09. Damage repair versus aging in biofilms. https://doi.org/10.1101/2020.01.08.899740

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A conserved cysteine-histidine-glutamate metal site identifies DUF501 (Rv1025), an essential uncharacterised protein family of Mycobacterium tuberculosis, as a candidate metalloenzyme and drug target

A substantial fraction of the Mycobacterium tuberculosis proteome remains functionally uncharacterised. Rv1025, a 155-residue protein carrying the domain of unknown function DUF501 (Pfam PF04417), is essential by transposon mutagenesis and vulnerable by CRISPR interference, an attractive but neglected drug target, yet has never been functionally described. The family (4,370 proteins, no Gene Ontology term, no solved structure) is uncharacterised across all organisms and essential in three Actinobacterial genera. A Foldseek search of the AlphaFold model against complete structural databases finds no significant homolog, indicating a novel fold. The operon eno-divIC-Rv1025-ppx2 is conserved across the Actinobacteria phylum, yet AlphaFold-Multimer finds no direct complex between Rv1025 and its neighbour DivIC. Instead, conservation across 8,700 homologous sequences reveals a near-invariant Cys113-His115-Glu59 cluster forming a pocket. Holo AlphaFold3 predictions with Zn, Fe and Mn confidently place a divalent metal on this triad at 2.25-2.47 A; mutating the triad relocates the metal, and an independent backbone-geometry predictor recovers the same site, confirming specificity. The triad is universal across the family: present in all 1,472 near-complete bacterial sequences of the Pfam alignment, with no non-conservative substitution among the 2,228 sequences examined, a defining feature of bacterial DUF501 rather than a mycobacterial peculiarity. We propose that DUF501 is a metal-binding protein and candidate metalloenzyme, the first functional hypothesis for this family, whose conserved, essential metal pocket is a promising drug target. As the predictions build on a conservation-defined site within a fully computational study, they are supportive rather than proof of metal occupancy and warrant experimental validation.

microbiology

Mycoplasmal endosymbionts of Trichomonas vaginalis are associated with reduced risk for Chlamydia trachomatis endometrial infection in asymptomatic, coinfected, women.

Trichomonas vaginalis is a protozoan parasite that causes trichomoniasis, the most common curable non-viral sexually transmitted infection, and Chlamydia trachomatis is a bacterial pathogen that can ascend to the upper genital tract and cause pelvic inflammatory disease, infertility, and ectopic pregnancy. T. vaginalis harbors bacterial endosymbionts, including Candidatus Malacoplasma girerdii, an obligate symbiont, and Metamycoplasma hominis, which can live freely or symbiotically. In a 16S rRNA sequencing study of the cervicovaginal microbiome of women at high risk for chlamydial infection, Ca. M. girerdii abundance was one of 13 features predicting lack of chlamydial spread to the endometrium, despite no direct association between T. vaginalis infection and reduced chlamydial ascension. Investigating the relationship between these microorganisms further, we found that T. vaginalis vaginal abundance correlated positively with chlamydial burden in women whose infection was confined to the cervix, while a nonsignificant inverse relationship was seen in women with endometrial spread. Among participants with high chlamydial burden, Ca. M. girerdii was detected exclusively in women without endometrial infection. Both endosymbionts trended toward more frequent detection, and higher abundance, in coinfected women without endometrial spread, while M. hominis abundance correlated strongly with T. vaginalis burden in this group. These findings suggest that mycoplasmal endosymbionts of T. vaginalis, rather than T. vaginalis itself, are microbial factors limiting chlamydial ascension, and point to a three-way interaction between parasite, endosymbiont, and bacterial pathogen that shapes upper genital tract C. trachomatis infection risk.

microbiology

Understanding the physiological alterations of Vibrio cholerae upon exposure to L-ascorbic acid

The scourge of cholera remains a major global public health threat. It affects up to 4 million people worldwide and causes tens of thousands of deaths each year. The disease is experiencing a concerning resurgence in many parts of Africa, the Middle East, and Asia. To effectively tackle cholera and circumvent rising antimicrobial resistance, targeted biological and preventive approaches, complementing traditional rehydration, are urgently needed. In this regard, our group has demonstrated the efficacy of L-ascorbic acid in controlling the growth and pathogenesis of Vibrio cholerae in vitro. The present work further provides a mechanistic elucidation of the L-ascorbic acid-mediated physiological changes in V. cholerae and also bolsters such a non-antibiotic approach to control cholera.

microbiology