inflammation (i.e., disease symptoms elicited by
enteropathogenic bacteria). This is attributable
to phage regulators, which link the bacterial
SOS response that is elicited by gut inflammation
to lytic induction and phage transfer. The process
operates in addition to inflammation-associated
bacterial blooms known to drive contact-dependent
plasmid transfer (fig. S8). The direct requirement
for inflammation implies that vaccination could
reduce phage transfer and thereby can be used
to slow down pathogen evolution.
From the pathogen’s perspective, the elicitation of gut inflammation has two different effects.
S. Tm growth is favored by the environmental
conditions provided by the inflamed gut (22, 25).
However, as inflammation produces many stressors (17, 26), it also stimulates the microbial SOS
response, induces the lytic cycle, and boosts horizontal gene transfer and reassortment of virulence factors, but also raises the risk of death
by lysis. From the perspective of the phage, the
link between lytic induction and the environmental cues of the inflamed gut may represent
an adaptation by amplifying phage copy numbers and increasing chances to reach novel bacterial hosts. It is also tempting to speculate that
the disease-accelerated phage transfer may explain
why enteropathogenic bacteria such as Salmonella
spp., Vibrio cholerae (27), or Shiga-toxin–producing
E. coli strains (28) harbor so many prophages
(1). It would be interesting to determine if such
disease-driven spread of temperate phages might
also affect the microbiota, e.g., by accelerating
the emergence of strains with increased virulence
in patients suffering from inflammatory bowel
diseases or AIDS (29, 30).
In conclusion, phage transfer is a dynamic
process occurring in vivo with variable frequencies. The host’s immune response was identified
as a key factor that can drastically affect its pace.
Notably, the innate (proinflammatory) and the
adaptive IgA response of the infected host have
opposing effects. Whereas gut inflammation (
elicited by the innate response of the naïve host)
boosts phage transfer, IgA-mediated mucosal
adaptive immunity slows it down. This highlights
an unexpected advantage of vaccination over antibiotic therapy, which is known to stimulate
phage transfer and generalized transduction (31).
This important beneficial aspect should receive
particular attention in future vaccination trials
and might open the door to managing pathogen
evolution, e.g., in farm animal reservoirs of zoo-notic enteropathogens.
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We are grateful to Hardt lab members and A. Buckling for
helpful discussions and to the RCHCI and EPIC team for excellent
support of our animal work. This work has been funded by
grants from the Swiss National Foundation (SNF, 310030_53074;
Sinergia CRSII_154414/1) and the Novartis FreeNovation program
to W.-D.H., the Swedish Research Council (2012-262;
2015-00635) to M.E.S., the SNF Ambizione fellowship
PZ00P3_136742 and a SNF Marie Heim-Vögtlin stipend to E.S.,
and an ETH Excellence Scholarship and Opportunity Program
stipend to E.B. The data presented in this study are in the main
text and in the supplementary materials.
Materials and Methods
Figs. S1 to S8
Tables S1 and S2
8 April 2016; accepted 22 February 2017
Mobile MUTE specifies subsidiary
cells to build physiologically
improved grass stomata
Michael T. Raissig,1 Juliana L. Matos,1 M. Ximena Anleu Gil,2 Ari Kornfeld,3
Akhila Bettadapur,2 Emily Abrash,1 Hannah R. Allison,1 Grayson Badgley,3
John P. Vogel,4 Joseph A. Berry,3 Dominique C. Bergmann1,2*
Plants optimize carbon assimilation while limiting water loss by adjusting stomatal
aperture. In grasses, a developmental innovation—the addition of subsidiary cells (SCs)
flanking two dumbbell-shaped guard cells (GCs)—is linked to improved stomatal
physiology. Here, we identify a transcription factor necessary and sufficient for SC
formation in the wheat relative Brachypodium distachyon. Unexpectedly, the transcription
factor is an ortholog of the stomatal regulator AtMUTE, which defines GC precursor fate
in Arabidopsis. The novel role of BdMUTE in specifying lateral SCs appears linked to its
acquisition of cell-to-cell mobility in Brachypodium. Physiological analyses on SC-less
plants experimentally support classic hypotheses that SCs permit greater stomatal
responsiveness and larger range of pore apertures. Manipulation of SC formation and
function in crops, therefore, may be an effective approach to enhance plant performance.
When plants colonized land and formed a cuticle to prevent desiccation, the evo- lution of adjustable pores—stomata—in the epidermis allowed plants to balance carbon dioxide uptake with water loss.
Stomata in today’s dicots resemble those of ~400
million years ago, consisting of two kidney-
shaped guard cells (GCs) (1, 2). Grasses, however,
have four-celled stomatal complexes with dumb-
bell shaped GCs flanked by two paracytic (lin-
eally unrelated) subsidiary cells (SCs) (Fig. 1, A
and B) (1–4). This cellular organization may en-
able fast adjustments of pore aperture at a low
energetic cost, while allowing higher gas-exchange
capacity (1, 2, 5), and may have contributed to
the successful diversification and dispersal of
the grass family during global aridification 30
to 45 million years ago (1, 2, 6).
Stomatal formation is limited to certain cell
files in the grass leaf epidermis (Fig. 1A, stage 1)
(3, 7). In Brachypodium distachyon, a stomatal initiation module—consisting of three basic helix-loop-helix (bHLH) transcription factors, BdICE1,
SCIENCE sciencemag.org 17 MARCH 2017 • VOL 355 ISSUE 6330 1215
1Department of Biology, Stanford University, 371 Serra Mall,
Stanford, CA 94305, USA. 2Howard Hughes Medical Institute
(HHMI), Stanford University, 371 Serra Mall, Stanford, CA 94305,
USA. 3Department of Global Ecology, Carnegie Institution for
Science, 260 Panama Street, Stanford, CA 94305, USA.
4U.S. Department of Energy Joint Genome Institute, 2800
Mitchell Drive, Walnut Creek, CA 94598, USA.
*Corresponding author. Email: firstname.lastname@example.org (M. T.R.);
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