MICROBE 2018 recap - Tiny Drivers of Evolution - HGT in Microbes

Dr. Michael Brockhurst, University of Sheffield
Causes and consequences of horizontal gene transfer (HGT) in microbes

We are now in the world of temperate phages...and one plasmid that we'll hear about later.

• Temperate phages have a two-stage life cycle, lytic and lysogenic (where they 'hide' by integrating in the genome and becoming a prophage).
• So what are the benefits of interacting and integrating temperate phages as a bacterium?
• Lots of horizontal gene transfer
• Accelerated evolutionary adaptation potential - how so?
• When you have phages jumping in and out of genomes leaving and taking DNA with them, you have the potential for mutational events and rearrangements...genes get turned on and off - this is all fuel for evolutionary adaptation (or just death, ya death can happen too).
• Increased competitiveness

Story Time...

Phage Vignette #1: Pseudomonas aeruginosa Liverpool epidemic strain (LES)

• Discovered in a CF unit in 1996
• It evolved to transfer patient to patient and spread rapidly turning into a superinfector that displaced any strain they already had by 2001.
• By 2004 it was causing increased morbidity
• In 2009 it's genome was sequenced and they found it "chock full" of mobile elements
• In 2010 it was found in Canada
• If you knock out the phage genes in LES then you decrease it's competitiveness in rat lung experiments so it appears to need the phages
• The genome contained 6 active prophages - this is not unusual in that many infections have a variable number of active prophages...2 to 6, it varies.
• So what's the deal with time? So after decades of these prophages being integrated into the genome if you activate them...do they still increase competitiveness? Rat lung experiments suggest yes. In fact the more lysogens you have the 'fitter' you are.
• Anotherwards, polylysogeny is fitter than single lysogeny

Phage Vignette #2: Phage Battles

• We live in a dog eat dog world and the realm of phages is not different.
• With multiple lysogens (prophages) you have multiple weapons but eventually you are going to immunize your competitor over time, negating your advantage.
• There are lots of factors impacting battles between phages and battles between phages and their prospective bacterial hosts in different environments:
• Phage killing
• Motility - living in 'gloopy' conditions which would promote loss of motility versus flowing conditions
• Differences in metabolism
• At first evolution is highly parallel until lysogeny is established (going to fixation rapidly) then you start having selective sweeps where the targets of selection start differing such that only genes evolving within the phage system are targeted and you end up finding a lot of the positively selected genes in phage genomes.
• For more information check out: Ecological conditions and extinction risk in co-evolving bacteria-phage populations
• For phi4 phage - this phage evolved the ability to jump into a genome and 'lock the door' so other phages could not infect promoting it's own survival and propagation.

For a nice introduction and overview of bacteriophages check out Sharma's 2017 paper in Folio Microbiologica

Other reading that might be of interest:

• What doesn't kill you makes you stronger!
• Lysogeny in Nature
• Bacteriophage resistance mechanisms
• Phages and interspecific competition
• Prophages that fight back
• Temperate phage weapons

And a short detour into HGT and plasmids...

• With plasmids it becomes a cost/benefit tradeoff in transfer because when you acquire a plasmid you are acquiring a lot of junk on top of some potentially helpful genes IF positive selection targets them thereby outweighing the cost of having the plasmid.
• So let's talk about mercury as an example...
• When you have no mercury in the system there is no invasion by the plasmid.
• When you select with mercury then you get an expansion of the bacteria that have the plasmid.

"Consistent with theoretical predictions, gene mobility via conjugation appeared to play a greater role in promoting plasmid stability under low-frequency pulses of Hg2+ selection. However, upon removal of Hg2+ selection, plasmids which had evolved under low-frequency pulse selective regimes declined over time. Our findings suggest that temporally variable selection environments, such as those created during antibiotic treatments, may help to explain the stability of mobile plasmid-encoded resistance." ~Stevenson et al., 2018

For more reading about plasmid stability in heterogenous environments check out this 2018 article from Harrison, Hall and Brockhurst.

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